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Eta statya o patogene viruse immunodeficita cheloveka O zabolevanii sm VICh infekciya o terminalnoj stadii bolezni sm Sindrom priobretyonnogo immunnogo deficita Zaprosy VICh i Vich perenapravlyayutsya syuda sm takzhe Vich znacheniya Vi rus immunodefici ta chelove ka VICh retrovirus iz roda lentivirusov vyzyvayushij medlenno progressiruyushee zabolevanie VICh infekciyu Virus immunodeficita chelovekaStilizovannoe izobrazhenie secheniya VIChNauchnaya klassifikaciyaGruppa VirusyRealm RiboviriaCarstvo PararnaviraeTip ArtverviricotaKlass RevtraviricetesPoryadok OrterviralesSemejstvo RetrovirusyPodsemejstvo Rod LentivirusyGruppa Primate lentivirus groupMezhdunarodnoe nauchnoe nazvaniePrimate lentivirus groupVidyHuman immunodeficiency virus 1 HIV 1 Virus immunodeficita cheloveka 1 VICh 1 Human immunodeficiency virus 2 HIV 2 Virus immunodeficita cheloveka 2 VICh 2 Gruppa po BaltimoruVI ocRNK OT virusySistematika v VikividahIzobrazheniya na VikiskladeNCBI 12721 Virus porazhaet kletki immunnoj sistemy imeyushie na svoej poverhnosti receptory CD4 T helpery monocity makrofagi kletki Langergansa dendritnye kletki kletki mikroglii V rezultate rabota immunnoj sistemy ugnetaetsya i razvivaetsya sindrom priobretyonnogo immunnogo deficita SPID organizm bolnogo teryaet vozmozhnost zashishatsya ot infekcij i opuholej voznikayut vtorichnye opportunisticheskie zabolevaniya kotorye ne harakterny dlya lyudej s normalnym immunnym statusom Lechenie VICh infekcii zaklyuchaetsya v priyome antiretrovirusnoj terapii kotoraya pozvolyaet VICh polozhitelnym lyudyam vesti normalnyj obraz zhizni a eyo kachestvo i prodolzhitelnost mozhet ne otlichatsya pri dolzhnoj terapii ot takovyh u VICh otricatelnyh lyudej Pri priyome ukazannoj terapii chelovek dostigaet neopredelyaemoj virusnoj nagruzki vsledstvie chego ne sposoben peredat infekciyu drugim lyudyam v tom chisle pri nezashishyonnom polovom akte takzhe terapiya pozvolyaet VICh polozhitelnym roditelyam estestvennym putyom zachat i rodit zdorovogo rebyonka V otsutstvie priyoma terapii progressiruyushaya VICh infekciya sposobna privesti k opportunisticheskim zabolevaniyam Otkrytie VIChIzobrazhenie sdelannoe rastrovym elektronnym mikroskopom V centre kadra zarazhyonnyj T limfocit Mnogochislennye svetlye kruglye vypuklosti na ego poverhnosti mesta sborki i otpochkovyvaniya virionov virusa immunodeficita chelovekaIzobrazhenie virionov poluchennoe pri pomoshi prosvechivayushego elektronnogo mikroskopa Vidno stroenie virionov vnutri kotoryh nahoditsya konusoobraznaya serdcevina V 1981 godu poyavilis pervye tri nauchnye stati o neobychnyh sluchayah razvitiya pnevmocistnoj pnevmonii i sarkomy Kaposhi u gomoseksualnyh muzhchin Do etogo oba zabolevaniya vstrechalis redko i byli harakterny dlya sovershenno raznyh grupp pacientov sarkomoj Kaposhi v osnovnom boleli pozhilye muzhchiny sredizemnomorskogo proishozhdeniya a pnevmocistnoj pnevmoniej pacienty s lejkozom posle intensivnoj himioterapii Poyavlenie etih zabolevanij svidetelstvuyushih o tyazhyolom immunodeficitnom sostoyanii u molodyh lyudej ne vhodyashih v sootvetstvuyushie gruppy riska nablyudalos vpervye Zatem obnaruzhili takie zhe simptomy sredi narkopotrebitelej bolnyh gemofiliej A i gaityan Naibolee znachimym bylo obnaruzhenie snizheniya sootnosheniya CD4 CD8 kletok v rezultate otnositelnogo i ili absolyutnogo umensheniya kolichestva CD4 limfocitov v sochetanii s uvelicheniem kolichestva CD8 limfocitov V iyule 1982 goda dlya oboznacheniya etogo sostoyaniya byl predlozhen termin sindrom priobretyonnogo immunnogo deficita SPID AIDS V sentyabre 1982 goda SPIDu bylo dano polnocennoe opredelenie kak nozologicheskoj forme na osnovanii nablyudeniya ryada opportunisticheskih infekcij u chetyryoh grupp pacientov ukazannyh vyshe V period s 1981 po 1984 god vyshlo neskolko rabot svyazyvayushih veroyatnost razvitiya SPIDa s analnym seksom ili s vliyaniem narkotikov Parallelno velis raboty nad gipotezoj o vozmozhnoj infekcionnoj prirode SPIDa Virus immunodeficita cheloveka byl otkryt v 1983 godu v dvuh laboratoriyah rabotavshih nezavisimo drug ot druga v Institute Pastera vo Francii pod rukovodstvom Lyuka Montane i v Nacionalnom institute raka v SShA pod rukovodstvom Roberta Gallo Rezultaty issledovanij v kotoryh iz tkanej pacientov s simptomami SPIDa vpervye udalos vydelit novyj retrovirus byli opublikovany 20 maya 1983 goda v zhurnale Science V etih zhe rabotah vydelennyj iz bolnyh SPIDom virus byl vpervye uspeshno razmnozhen v kultiviruemyh T limfocitah Francuzskaya gruppa issledovatelej pokazala chto serologicheski etot virus otlichaetsya ot HTLV I i nazvala ego LAV virus associirovannyj s limfadenopatiej a amerikanskaya gruppa nazvala ego HTLV III oshibochno otnesya k gruppe HTLV virusov Issledovateli vydvinuli predpolozhenie chto virus mozhet vyzyvat sindrom priobretyonnogo immunnogo deficita V 1986 godu bylo dokazano chto virusy otkrytye v 1983 francuzskimi i amerikanskimi issledovatelyami geneticheski identichny Pervonachalnye nazvaniya virusov byli uprazdneny i predlozheno odno obshee nazvanie virus immunodeficita cheloveka V 2008 godu Lyuk Montane i Fransuaza Barr Sinussi byli udostoeny Nobelevskoj premii v oblasti fiziologii ili mediciny za otkrytie virusa immunodeficita cheloveka VICh infekciyaInficirovanie Osnovnaya statya Inficirovanie virusom immunodeficita cheloveka Virus mozhet peredavatsya cherez pryamoj kontakt povrezhdyonnoj ili nepovrezhdyonnoj slizistoj obolochki ili povrezhdyonnoj kozhi zdorovogo cheloveka s biologicheskimi zhidkostyami zarazhyonnogo cheloveka krovyu predsemennoj zhidkostyu vydelyayushejsya na protyazhenii vsego polovogo akta spermoj sekretom vlagalisha grudnym molokom Peredacha virusa mozhet proishodit pri nezashishyonnom analnom vaginalnom ili oralnom sekse Intaktnaya nepovrezhdyonnaya kozha yavlyaetsya effektivnym barerom dlya infekcii tak kak v kozhe otsutstvuyut kletki kotorye mogut byt zarazheny VICh Dlya uspeshnoj infekcii trebuetsya pryamoj kontakt s krovenosnoj sistemoj ili s membranami kletok slizistyh obolochek Slizistye obolochki polovyh organov i pryamoj kishki chasto poluchayut neznachitelnye povrezhdeniya pri polovom akte cherez kotorye virus mozhet pronikat v krov Takie povrezhdeniya chashe voznikayut pri nalichii zabolevanij peredayushihsya polovym putyom naprimer v sluchae gerpesa Poetomu osobenno opasnoj formoj polovogo akta dlya prinimayushego partnyora yavlyaetsya nezashishyonnyj analnyj seks tak kak pri etoj forme voznikaet naibolshee chislo melkih i krupnyh povrezhdenij S drugoj storony zarazhenie vozmozhno i v sluchae nepovrezhdyonnoj slizistoj obolochki tak kak slizistaya soderzhit znachitelnoe kolichestvo dendritnyh kletok v tom chisle kletok Langergansa kotorye mogut igrat rol perenoschikov virusnyh chastic v limfaticheskie uzly Peredacha virusa proishodit s bolshej veroyatnostyu pri ispolzovanii zarazhyonnyh igl i shpricev osobenno potrebitelyami inekcionnyh narkotikov a takzhe pri perelivanii krovi v sluchae narusheniya medicinskim personalom ustanovlennyh procedur proverki donorskoj krovi Takzhe peredacha virusa mozhet proizojti mezhdu materyu i rebyonkom vo vremya beremennosti rodov zarazhenie cherez krov materi i pri grudnom vskarmlivanii prichyom kak ot zarazhyonnoj materi k zdorovomu rebyonku cherez grudnoe moloko tak i ot zarazhyonnogo rebyonka k zdorovoj materi cherez pokusyvanie grudi vo vremya kormleniya Virus ne peredayotsya vozdushno kapelnym putyom bytovym putyom pri soprikosnovenii s nepovrezhdyonnoj kozhej cherez ukusy bolshinstva krovososushih nasekomyh isklyuchenie sostavlyayut muhi zhigalki net v istochnike obs slyozy i slyunu iz za togo chto koncentraciya virionov VICh v etih zhidkostyah nizhe inficiruyushej dozy a takzhe iz za togo chto slyuna agressivnaya sreda razrushayushaya svoimi fermentami viriony VICh Virus ne stoek vo vneshnej srede bystro pogibaet pod pryamymi solnechnymi luchami pri temperature vyshe 57 C i prakticheski momentalno pri 100 C takzhe virus ochen chuvstvitelen k kislotnosti on mozhet vyzhit tolko pri pH ot 7 do 8 shelochnym i solyonym sredam Bolezn Osnovnaya statya VICh infekciya Dinamika kolichestva CD4 limfocitov i kopij RNK virusa za period ot momenta inficirovaniya do terminalnoj stadii kolichestvo CD4 limfocitov v 1 mkl krovi kolichestvo kopij RNK virusa v 1 ml plazmy krovi V techenie bolezni vydelyayut tri stadii ostruyu infekciyu latentnyj period i terminalnuyu stadiyu SPID sm illyustraciyu V hode razvitiya VICh infekcii u odnogo i togo zhe cheloveka v rezultate mutacij voznikayut novye shtammy virusa kotorye razlichayutsya po skorosti vosproizvedeniya i sposobnosti inficirovat Razmnozhivshis virusnye chasticy vysvobozhdayutsya iz porazhyonnyh kletok i vnedryayutsya v novye cikl razvitiya povtoryaetsya Inficirovannye virusom T helpery postepenno gibnut iz za razrusheniya virusom apoptoza ili unichtozheniya T killerami V processe razvitiya VICh infekcii kolichestvo CD3 CD4 limfocitov snizhaetsya nastolko chto organizm uzhe ne mozhet protivostoyat vozbuditelyam opportunisticheskih infekcij kotorye neopasny ili malo opasny dlya zdorovyh lyudej s normalno funkcioniruyushej immunnoj sistemoj Prichiny snizheniya mogut byt razlichnymi 1 pereraspredelenie prolimfocitov v storonu CD3 CD8 ili estestvennyh killerov vyzyvaemoe naprimer gerpesom 4go tipa 2 komplimentarnost gp120 i receptora CD4 vyzyvaet autoimunnuyu reakciyu vyrabotku antitel razrushayushih CD3 CD4 limfocit nalichie dannogo belka neobhodimo opredelyat s uchyotom pogreshnosti test sistem 3 soputstvuyushimi zabolevaniyami ugnetayushimi kostnyj mozg ili organy krovetvoreniya timus limfaticheskuyu sistemu Soglasno svedeniyam ob issledovaniyah dannoj problemy tolko okolo 4 CD3 CD4 limfocitov porazhaetsya virusom Prichem neobhodimo ponimat chto CD3 CD4 i CD3 CD8 limfocity eto postoyanno vyrabatyvaemye organizmom kletki iz prolimfocitov organizm sam reguliruet kakoj prolimfocit stanet CD4 CD8 ili estestvennym killerom Na terminalnoj stadii SPID oslablennyj organizm porazhayut bakterialnye gribkovye virusnye i protozojnye infekcii a takzhe opuholi V otsutstvie antiretrovirusnoj terapii smert pacienta nastupaet ne v rezultate razmnozheniya virusa v CD4 kletkah a po prichine razvitiya opportunisticheskih zabolevanij vtorichnyh po otnosheniyu k VICh infekcii Epidemiologiya Osnovnaya statya Epidemiologiya VICh infekcii Po dannym na 2011 god v mire za vsyo vremya VICh infekciej zaboleli 60 millionov chelovek iz nih 25 millionov umerli a 35 millionov zhivut s VICh infekciej Bolee dvuh tretej iz nih prozhivayut v Afrike k yugu ot pustyni Sahara Epidemiya nachalas zdes v konce 1970 h nachale 1980 h Zatem epidemiya perekinulas v SShA Zapadnuyu Evropu i strany Yuzhnoj Afriki Segodnya za isklyucheniem stran Afriki bystree vsego virus rasprostranyaetsya v Centralnoj Azii i Vostochnoj Evrope v tom chisle v Rossii Epidemicheskaya situaciya v etih regionah sderzhivalas do konca 1990 h zatem s 1999 po 2002 gody kolichestvo inficirovannyh pochti utroilos v osnovnom za schyot inekcionnyh narkomanov Znachitelno nizhe srednego VICh infekciya rasprostranena v Vostochnoj Azii Severnoj Afrike i na Blizhnem Vostoke V masshtabe planety epidemicheskaya situaciya stabilizirovalas kolichestvo novyh sluchaev VICh infekcii snizilos s 3 5 milliona v 1997 godu do 2 7 milliona v 2007 godu Po dannym na konec 2016 goda v Rossii 848 tysyach chelovek zhivut s VICh infekciej za period s 1986 po 2016 god umerlo ot raznyh prichin 220 tysyach VICh inficirovannyh grazhdan Rossii podrobnee sm Statistika zabolevaemosti i smertnosti po Rossii Diagnostika Osnovnaya statya Test na VICh Analiz krovi pozvolyaet obnaruzhit antitela k belkam virusa IFA reakciyu antitel na belki virusa vestern blot RNK virusa OT PCR Opredelenie virusnoj nagruzki podschyot kolichestva kopij RNK virusa v millilitre plazmy krovi pozvolyaet sudit o stadii zabolevaniya i effektivnosti lecheniya Obyazatelnaya proverka donorskoj krovi v razvityh stranah v znachitelnoj stepeni sokratila vozmozhnost peredachi virusa pri eyo ispolzovanii Testirovanie na VICh beremennyh zhenshin pozvolyaet svoevremenno nachat priyom lekarstv i rodit zdorovogo rebyonka Sushestvuet mnenie chto prinuditelnoe testirovanie naseleniya besperspektivno s tochki zreniya sderzhivaniya epidemii i narushaet prava cheloveka V Rossii provedenie testa bez soglasiya cheloveka yavlyaetsya nezakonnym odnako sushestvuyut situacii v kotoryh predostavlenie rezultatov testirovaniya na VICh yavlyaetsya obyazatelnym no ne nasilstvennym donorstvo trudoustrojstvo medicinskih rabotnikov dlya inostrannyh grazhdan poluchayushih razreshenie na prebyvanie v RF v mestah lisheniya svobody pri nalichii klinicheskih pokazanij Lechenie Osnovnaya statya Antiretrovirusnaya terapiya Na 2022 god izvestno o chetyryoh sluchayah izlecheniya ot virusa Tri iz nih v medicinskoj literature figuriruyut pod prozvishami Berlinskij Londonskij i San Paulskij pacienty effekt v ih sluchayah byl dostignut pri pomoshi peresadki kostnogo mozga donorskie kletki soderzhali mutaciyu CCR5 D32 delayushuyu ih nevospriimchivymi k VICh V nachale 2022 goda stalo izvestno o chetvyortom cheloveke kotoryj izlechilsya ot VICh na etot raz s pomoshyu transplantacii kletok pupovinnoj krovi soderzhashih mutaciyu CCR5 D32 V marte 2023 goda v zhurnale Cell vyshla statya opisyvayushaya dannyj sluchaj Iz 35 millionov chelovek zhivushih s VICh infekciej chast ostayotsya v zhivyh blagodarya antiretrovirusnoj terapii V sluchae otsutstviya antiretrovirusnoj terapii VICh infekcii smert nastupaet v srednem cherez 9 11 let posle zarazheniya Pri provedenii antiretrovirusnoj terapii prodolzhitelnost zhizni pacienta sostavlyaet 70 80 let Antiretrovirusnye preparaty meshayut VICh razmnozhatsya v kletkah immunnoj sistemy cheloveka blokiruya vnedrenie virionov v kletki i narushaya na raznyh etapah process sborki novyh virionov Svoevremenno nachatoe lechenie antiretrovirusnymi preparatami v sotni raz snizhaet risk razvitiya SPIDa i posleduyushej smerti Antiretrovirusnye preparaty u chasti pacientov vyzyvayut pobochnye effekty v nekotoryh sluchayah dazhe trebuyushie smenit shemu lecheniya nabor prinimaemyh lekarstv Terapiyu naznachayut pri snizhenii immuniteta i ili vysokoj virusnoj nagruzke Esli chislo CD4 limfocitov veliko i virusnaya nagruzka nizkaya terapiyu ne naznachayut Posle naznacheniya terapii lekarstva nuzhno prinimat ezhednevno v odno i to zhe vremya i pozhiznenno chto sozdayot neudobstva dlya pacientov Krome togo sleduet uchityvat vysokuyu stoimost mesyachnogo kursa lekarstv V 2014 godu neobhodimye lekarstva poluchali menee poloviny iz 9 5 mln chelovek nuzhdayushihsya v protivovirusnoj terapii Takzhe vse beremennye zhenshiny s VICh infekciej dolzhny nachinat nezamedlitelnuyu ARVT dlya predotvrasheniya peredachi VICh plodu Soglasno rekomendaciyam VOZ ARVT sleduet nezamedlitelno nachinat vsem VICh inficirovannym detyam do polutora let Nachalo terapii u detej poluchivshih VICh ot materi v techenie 3 mesyacev posle rodov snizhaet smertnost na 75 V otsutstvie lecheniya tret VICh inficirovannyh detej umiraet v techenie pervogo goda zhizni i 50 v techenie vtorogo goda Esli diagnostika VICh nevozmozhna lechenie sleduet nachinat v vozraste 9 mesyacev libo ranee v sluchae poyavleniya simptomov Po sostoyaniyu na fevral 2016 goda bylo obyavleno chto gruppe nemeckih uchyonyh udalos polnostyu udalit tip VICh 1 iz zhivyh kletok Ispytaniya provodilis na kletkah cheloveka vzhivlyonnyh podopytnym mysham Ispytaniya na lyudyah dolzhny provoditsya v blizhajshee vremya V 2018 godu Administraciej po kontrolyu nad produktami i lekarstvami FDA byl odobren ibalizumab ibalizumab uiyk dlya primeneniya v terapii pacientov s multirezistentnym VICh 1 Preparat predstavlyaet soboj monoklonalnoe antitelo kotoroe svyazyvaetsya s CD4 receptorami T kletok i podavlyaet process proniknoveniya virusa v kletku cheloveka Ibalizumab mozhet primenyatsya v terapii s drugimi antiretrovirusnymi lekarstvami Po rezultatam klinicheskih issledovanij s uchastiem 40 pacientov ranee proshedshih lechenie bolee chem 10 razlichnymi antiretrovirusnymi agentami virusnaya nagruzka snizilas u bolshinstva ispytuemyh cherez odnu nedelyu posle vvedeniya pervoj dozy preparata Cherez 24 nedeli terapii virusologicheskaya supressiya byla dostignuta u 43 uchastnikov klinicheskih ispytanij VICh v 2019 godu vnosili v spisok desyati osnovnyh problem zdravoohraneniya kotorye trebuyut osobogo vnimaniya VOZ KlassifikaciyaOsnovnaya statya Lentivirusy Virus immunodeficita cheloveka otnosyat k semejstvu retrovirusov Retroviridae rodu lentivirusov Lentivirus Nazvanie Lentivirus proishodit ot latinskogo slova lente medlennyj Takoe nazvanie otrazhaet odnu iz osobennostej virusov etoj gruppy a imenno medlennuyu i neodinakovuyu skorost razvitiya infekcionnogo processa v makroorganizme Dlya lentivirusov takzhe harakteren dlitelnyj inkubacionnyj period Dlya virusa immunodeficita cheloveka harakterna vysokaya chastota geneticheskih izmenenij voznikayushih v processe samovosproizvedeniya Chastota vozniknoveniya oshibok u VICh sostavlyaet 10 3 10 4 oshibok na genom na cikl replikacii chto na neskolko poryadkov bolshe analogichnoj velichiny u eukariot Razmer genoma VICh sostavlyaet primerno 104nukleotidov Iz etogo sleduet chto prakticheski kazhdyj dochernij genom hotya by na odin nukleotid otlichaetsya ot svoego predshestvennika V sovremennoj klassifikacii razlichayut dva osnovnyh vida VICh VICh 1 i VICh 2 Predpolagaetsya chto eti virusy voznikli v rezultate nezavisimoj peredachi lyudyam SIV virusa immunodeficita obezyan ot shimpanze i mangabeev sootvetstvenno I VICh 1 i VICh 2 sposobny vyzyvat seryoznyj immunodeficit odnako klinicheskoe techenie bolezni neskolko razlichaetsya Izvestno chto VICh 2 menee patogenen i peredayotsya s menshej veroyatnostyu chem VICh 1 Veroyatno eto svyazano s tem chto VICh 2 infekciya harakterizuetsya bolee nizkim chislom virusnyh chastic na millilitr krovi Otmecheno chto infekciya VICh 2 obespechivaet nositelyu nebolshuyu zashitu ot zarazheniya VICh 1 Odnako opisany sluchai dvojnoj infekcii prichyom zarazhenie mozhet proishodit v lyubom poryadke Infekciya VICh 2 rezhe zakanchivaetsya razvitiem SPIDa Est svedeniya o neskolko bolshej chastote razvitiya sarkomy Kaposhi kandidoza rotovoj polosti i hronicheskoj lihoradki pri VICh 1 SPIDe Pri VICh 2 SPIDe chashe razvivaetsya encefalit hronicheskaya ili bakterialnaya diareya seryoznye citomegalovirusnye infekcii i holangit K rodu Lentivirus takzhe otnosyat vidy vyzyvayushie shozhie zabolevaniya u obezyan koshek loshadej ovec i t d VICh 1 VICh 1 opisan v 1983 godu i yavlyaetsya naibolee rasprostranyonnym i patogennym vidom VICh Globalnaya epidemiya VICh infekcii glavnym obrazom obuslovlena rasprostraneniem VICh 1 V podavlyayushem bolshinstve sluchaev esli ne ogovoreno inache pod VICh podrazumevayut VICh 1 Vid VICh 1 klassificiruyut na glavnuyu gruppu M i neskolko pobochnyh grupp Schitaetsya chto gruppy M N O P obrazovalis v rezultate nezavisimyh sluchaev peredachi SIV ot obezyany k cheloveku i posleduyushej mutacii virusa do VICh Virusy gruppy M angl main osnovnaya yavlyayutsya prichinoj bolee 90 sluchaev VICh infekcii Gruppu M klassificiruyut na neskolko klad nazyvaemyh podtipami takzhe oboznachaemyh bukvami podtip A shiroko rasprostranyon naprimer v Zapadnoj Afrike i Rossii podtip B dominiruet v Evrope Severnoj Amerike Yuzhnoj Amerike Yaponii Tailande Avstralii podtip C preobladaet v Yuzhnoj i Vostochnoj Afrike Indii Nepale nekotoryh chastyah Kitaya podtip D obnaruzhen tolko v Vostochnoj i Centralnoj Afrike podtip E ne byl vyyavlen v nerekombinantnom vide lish sovmestno s podtipom A kak CRF01 AE v Yugo Vostochnoj Azii podtip F vyyavlen v Centralnoj Afrike Yuzhnoj Amerike i Vostochnoj Evrope podtip G i rekombinantnaya forma CRF02 AG vyyavleny v Afrike i Centralnoj Evrope podtip H obnaruzhen tolko v Centralnoj Afrike podtip I byl predlozhen dlya opisaniya shtamma produkta mnozhestvennoj rekombinacii CRF04 cpx neskolkih podtipov podtip J rasprostranyon v Severnoj Centralnoj i Zapadnoj Afrike i stranah Karibskogo bassejna podtip K obnaruzhen tolko v Kongo i Kamerune podtip L obnaruzhen v Kongo Gruppa O angl outlier nepohozhij obnaruzhena v Centralnoj Afrike i Zapadnoj Afrike Naibolee rasprostranena v Kamerune gde v 1997 godu bolee 2 pacientov byli zarazheny virusom gruppy O okolo 100 000 chelovek po dannym na 2013 god Virusy etoj gruppy ne opredelyalis rannimi versiyami test sistem na VICh 1 sovremennye testy opredelyayut virusy i gruppy O i gruppy N Gruppa N angl non M non O ni M ni O oboznachaet shtammy ne M i ne O opisana v 1998 godu i obnaruzhena tolko v Kamerune S 2006 goda vyyavleny lish 10 zarazhenij virusami gruppy N Gruppa P v 2009 godu byla opredelena nukleotidnaya posledovatelnost RNK VICh znachitelno shodnaya s virusom immunodeficita obezyan opisannym u gorill SIVgor no ne s SIV harakternym dlya shimpanze SIVcpz Virus byl vydelen iz obrazcov poluchennyh ot zhenshiny kamerunskogo proishozhdeniya prozhivayushej vo Francii VICh 2 VICh 2 identificirovan v 1986 godu geneticheski ochen blizok k T limfotropnomu virusu SIV i v menshej stepeni k virusu VICh 1 Genomy VICh 1 i VICh 2 imeyut gomologiyu konservativnyh genov gag i pol okolo 60 i do 45 dlya genov belkov obolochki Po sostoyaniyu na 2010 god opisano 8 grupp VICh 2 lish gruppy A i B yavlyayutsya epidemicheskimi Virusy gruppy A rasprostraneny v Zapadnoj Afrike Angole Mozambik Brazilii Indii i malo rasprostraneny v SShA i Evrope Virusy gruppy V rasprostraneny v Zapadnoj Afrike Stroenie virionaStroenie virusa immunodeficita cheloveka Viriony VICh imeyut vid sfericheskih chastic diametr kotoryh sostavlyaet okolo 100 120 nanometrov Eto priblizitelno v 60 raz menshe diametra eritrocita V sostav zrelyh virionov vhodit neskolko tysyach belkovyh molekul razlichnyh tipov Kapsid zrelogo viriona sostoyashij iz primerno 2000 molekul belka r24 imeet formu usechyonnogo konusa Vnutri kapsida nahoditsya belkovo nukleinovyj kompleks dve niti virusnoj RNK prochno svyazannye s belkom nukleokapsida p7 fermenty obratnaya transkriptaza proteaza integraza S kapsidom takzhe associirovany belki Nef i Vif 7 20 molekul Vif na virion Vnutri viriona i veroyatnee vsego za predelami kapsida obnaruzhen belok Vpr 8 11 Krome togo s kapsidom VICh 1 no ne VICh 2 svyazany okolo 200 kopij kletochnogo fermenta angl ciklofilin A neobhodimogo dlya sborki viriona Kapsid okruzhyon obolochkoj obrazovannoj primerno 2000 molekul matriksnogo belka p17 Matriksnaya obolochka v svoyu ochered okruzhena dvuslojnoj lipidnoj membranoj yavlyayushejsya naruzhnoj obolochkoj virusa Ona obrazovana molekulami fosfolipidov zahvachennymi virusom vo vremya ego otpochkovyvaniya ot kletki v kotoroj on sformirovalsya V lipidnuyu membranu vstroeny 72 glikoproteinovyh kompleksa Env kazhdyj iz kotoryh obrazovan tremya molekulami transmembrannogo glikoproteina gp41 TM sluzhashego yakorem kompleksa i tremya molekulami poverhnostnogo glikoproteina gp120 SU S pomoshyu belka gp120 virus prisoedinyaetsya k receptoru CD4 i koreceptoru nahodyashimsya na poverhnosti T limfocitov cheloveka Stehiometricheskoe sootnoshenie p24 gp120 v virione sostavlyaet 60 100 1 11 Pri formirovanii naruzhnoj obolochki virusa takzhe proishodit zahvat nekotorogo kolichestva membrannyh belkov kletki v tom chisle chelovecheskih lejkocitarnyh antigenov HLA klassov I i II i molekul adgezii Belki viriona intensivno izuchayutsya poskolku yavlyayutsya mishenyami razrabatyvaemyh lekarstv i vakciny protiv VICh Funkcii vazhnyh strukturnyh belkov VICh 1 Sokrashenie Opisanie Funkciigp41 TM transmembrane Transmembrannyj glikoprotein massoj 41 kDa Raspolagaetsya vo vneshnem sloe lipidnoj membrany igraet rol yakorya uderzhivayushego molekuly belka gp120gp120 SU surface Glikoprotein massoj 120 kDa Naruzhnyj belok viriona Nekovalentno svyazan s transmembrannym belkom gp41 S odnoj molekuloj gp41 svyazany 3 5 molekul gp120 Sposoben svyazyvat receptor CD4 Igraet vazhnuyu rol v processe proniknoveniya virusa v kletku p24 CA capsid Belok massoj 24 kDa Obrazuet kapsid virusap17 MA matrix Matriksnyj belok massoj 17 kDa Okolo dvuh tysyach molekul etogo belka obrazuyut sloj tolshinoj 5 7 nm raspolagayushijsya mezhdu vneshnej obolochkoj i kapsidom virusa p7 NC nucleocapsid Nukleokapsidnyj belok massoj 7 kDa Vhodit v sostav kapsida virusa Obrazuet kompleks s virusnoj RNK Genom i kodiruemye belkiGenom VICh 1 Geneticheskij material VICh predstavlen dvumya kopiyami polozhitelno smyslovoj RNK Genom VICh 1 imeet dlinu 9000 nukleotidov Koncy genoma predstavleny dlinnymi koncevymi povtorami kotorye upravlyayut produkciej novyh virusov i mogut aktivirovatsya i belkami virusa i belkami inficirovannoj kletki 9 genov VICh 1 kodiruyut po krajnej mere 15 belkov Gen pol kodiruet fermenty obratnuyu transkriptazu RT integrazu IN i proteazu PR Gen gag kodiruet poliprotein Gag p55 rassheplyaemyj virusnoj proteazoj do strukturnyh belkov p6 p7 p17 p24 Gen env kodiruet belok gp160 rassheplyaemyj kletochnoj endoproteazoj furinom na strukturnye belki gp41 i gp120 8 12 Drugie shest genov tat rev nef vif vpr vpu vpx u VICh 2 kodiruyut belki otvechayushie za sposobnost VICh 1 inficirovat kletki i proizvodit novye kopii virusa Replikaciya VICh 1 in vitro vozmozhna bez genov nef vif vpr vpu odnako ih produkty neobhodimy dlya polnocennoj infekcii in vivo Gag Poliprotein predshestvennik Gag p55 sinteziruetsya s polnorazmernoj genomnoj RNK kotoraya v dannom sluchae sluzhit v kachestve mRNK v processe standartnoj kep zavisimoj translyacii no vozmozhna i IRES zavisimaya translyaciya Predshestvenniki funkcionalnyh belkov raspolagayutsya v sostave poliproteina Gag p55 v sleduyushem poryadke p17 p24 p2 p7 p1 p6 8 r1 i r2 soedinitelnye peptidy drugie produkty rasshepleniya Gag p55 opisany vyshe Nerassheplyonnyj proteazoj Gag p55 soderzhit tri osnovnyh domena domen membrannoj lokalizacii M membrane targeting domen vzaimodejstviya I interaction i pozdnij domen L late Domen M raspolozhennyj vnutri oblasti p17 MA miristiliruetsya prisoedinyayutsya ostatki miristinovoj kisloty i napravlyaet Gag p55 k plazmaticheskoj membrane Domen I nahodyashijsya vnutri oblasti p7NC NC nucleocapsid otvechaet za mezhmolekulyarnye vzaimodejstviya otdelnyh monomerov Gag p55 Domen L takzhe lokalizovannyj v oblasti p7NC oposreduet otpochkovyvanie virionov ot plazmaticheskoj membrany v etom processe uchastvuet takzhe r6 oblast poliproteina Gag p55 8 Vpu Dvumya vazhnymi funkciyami belka Vpu yavlyayutsya 1 razrushenie kletochnogo receptora CD4 v endoplazmaticheskom retikulume putyom privlecheniya ubikvitinligaznyh kompleksov i 2 stimulyaciya vydeleniya dochernih virionov iz kletki putyom inaktivacii interferon induciruemogo transmembrannogo belka CD317 BST 2 poluchivshego takzhe nazvanie tetherin za ego sposobnost podavlyat vydelenie vnov obrazovavshihsya dochernih virionov posredstvom ih uderzhaniya na poverhnosti kletki Vpr Belok Vpr neobhodim dlya replikacii virusa v nedelyashihsya kletkah v tom chisle makrofagah Etot belok naryadu s drugimi kletochnymi i virusnymi belkami aktiviruet transkripciyu s ispolzovaniem dlinnyh koncevyh povtorov genoma VICh v kachestve promotorov Belok Vpr igraet vazhnuyu rol v perenose virusnoj DNK v yadro i vyzyvaet zaderzhku deleniya kletki v periode G2 Vif Belok Vif igraet vazhnuyu rol v podderzhke replikacii virusa Vif induciruet ubikvitinilirovanie i degradaciyu kletochnogo antivirusnogo belka APOBEC3G kotoryj vyzyvaet deaminirovanie DNK privodyashee k mutacionnym zamenam G na A v virusnoj DNK sinteziruemoj v hode obratnoj transkripcii Shtammy lishyonnye Vif ne repliciruyutsya v CD4 limfocitah nekotoryh liniyah T limfocitov i makrofagah Eti shtammy sposobny pronikat v kletki misheni i nachinat obratnuyu transkripciyu odnako sintez virusnoj DNK ostayotsya nezavershyonnym Nef Belok Nef vypolnyaet neskolko funkcij On podavlyaet ekspressiyu molekul CD4 i HLA klassov I i II na poverhnosti inficirovannyh kletok i tem samym pozvolyaet virusu uskolzat ot ataki citotoksicheskih T limfocitov i ot raspoznavaniya CD4 limfocitami Belok Nef mozhet takzhe ugnetat aktivaciyu T limfocitov svyazyvaya razlichnye belki komponenty sistem vnutrikletochnoj peredachi signala U inficirovannyh virusom immunodeficita makak rezusov aktivnaya replikaciya virusa i progressirovanie bolezni vozmozhny tolko pri intaktnom gene nef Delecii gena nef byli obnaruzheny v shtammah VICh vydelennyh u gruppy avstralijcev s dlitelnym neprogressiruyushim techeniem infekcii Odnako u chasti iz nih so vremenem poyavilis priznaki progressirovaniya infekcii v tom chisle snizhenie chisla CD4 limfocitov Takim obrazom hotya delecii gena nef i mogut zamedlyat replikaciyu virusa eto ne garantiruet polnoj nevozmozhnosti progressirovaniya zabolevaniya Tat i Rev Regulyatornye belki Tat trans aktivator i Rev nakaplivayutsya v yadre kletki i svyazyvayut opredelyonnye uchastki virusnoj RNK Belok Tat imeet molekulyarnuyu massu okolo 14 15 kDa svyazyvaet vtorichnuyu strukturu genomnoj RNK vblizi 5 netransliruemoj oblasti aktiviruet obratnuyu transkripciyu genomnoj RNK VICh sintez virusnyh mRNK neobhodim dlya replikacii virusa pochti vo vseh kulturah kletok reguliruet vyhod virionov iz zarazhyonnyh kletok nuzhdaetsya v kletochnom kofaktore cikline T1 Belok Rev reguliruet ekspressiyu belkov viriona svyazyvaet mRNK gena env v oblasti RRE angl Rev response element introna razdelyayushego ekzony genov Tat i Rev Belki Tat i Rev stimuliruyut transkripciyu provirusnoj DNK i iz yadra v citoplazmu a takzhe neobhodimy dlya translyacii Belok Rev obespechivaet takzhe transport komponentov virusa iz yadra i pereklyuchenie sinteza regulyatornyh belkov virusa na sintez strukturnyh Zhiznennyj ciklDo proniknoveniya v kletku mishen Posle popadaniya virionov VICh na poverhnost i vnutr organizma virusnye chasticy okazyvayutsya v razlichnyh po svoej agressivnosti biologicheskih zhidkostyah Slyuna i zheludochnyj sok soderzhat fermenty kotorye v bo lshej stepeni razrushayut viriony VICh chem drugie biologicheskie zhidkosti eto ne otnositsya k mladencam pervyh mesyacev zhizni u kotoryh eshyo ne vyrabatyvayutsya sootvetstvuyushie fermenty pishevareniya iz za chego mladency mogut byt zarazheny cherez grudnoe moloko Viriony VICh pronikayut v krovenosnuyu i limfaticheskuyu sistemu organizma i peremeshayutsya po organizmu v potoke krovi i limfy Okazavshis ryadom s CD4 kletkoj viriony VICh prisoedinyayutsya k receptoru CD4 na eyo plazmaticheskoj membrane Proniknovenie v kletku i obratnaya transkripciya Mehanizm sliyaniya viriona VICh i plazmaticheskoj membrany T limfocita cheloveka 1 Vzaimodejstvie virusnogo belka gp120 s kletochnym receptorom CD4 ukazano krasnoj strelkoj 2 Konformacionnye izmeneniya virusnogo belka gp120 obespechivayut svyazyvanie s kletochnym receptorom CCR5 ukazano krasnoj strelkoj 3 Koncevye uchastki virusnogo belka gp41 pronikayut v plazmaticheskuyu membranu kletki ukazano krasnoj strelkoj 4 Virusnyj belok gp41 podvergaetsya znachitelnym konformacionnym izmeneniyam ukazano krasnoj strelkoj chto privodit k sblizheniyu i sliyaniyu membran viriona i kletki Virusnyj glikoprotein gp120 prochno svyazyvaet receptor CD4 V rezultate takogo vzaimodejstviya gp120 preterpevaet konformacionnye izmeneniya kotorye pozvolyayut emu takzhe svyazat molekulu koreceptora CXCR4 ili CCR5 ekspressiruemyh na poverhnosti T limfocitov makrofagov dendritnyh kletok i mikroglii V zavisimosti ot sposobnosti svyazyvat eti koreceptory VICh klassificiruyut na R5 tropnye svyazyvayut tolko koreceptor CCR5 X4 tropnye svyazyvayut tolko koreceptor CXCR4 i R5X4 tropnye mogut vzaimodejstvovat s oboimi koreceptorami varianty Pri zarazhenii v osnovnom peredayutsya R5 tropnye i R5X4 tropnye varianty Preparaty blokiruyushie koreceptory mogut byt effektivny protiv VICh Posle opisannyh sobytij virusnyj belok gp41 pronikaet v membranu kletki i podvergaetsya znachitelnym konformacionnym izmeneniyam vsledstvie kotoryh membrana kletki i membrana viriona VICh sblizhayutsya drug s drugom i zatem slivayutsya Virusnyj belok gp41 ochen vazhen dlya sliyaniya membran poetomu ego rassmatrivayut v kachestve misheni dlya razrabotki protivovirusnyh preparatov Posle sliyaniya membran soderzhimoe viriona pronikaet vnutr kletki Vnutri kletki virusnaya RNK vysvobozhdaetsya iz kapsida Zatem pod dejstviem obratnoj transkriptazy proishodit obratnaya transkripciya process sinteza DNK na osnovanii informacii v odnocepochechnoj genomnoj RNK virusa Bolshaya chast lekarstvennyh preparatov odobrennyh dlya primeneniya pri VICh infekcii napravlena na narushenie raboty obratnoj transkriptazy Transport virusnoj DNK v yadro i integraciya v genom Posle zaversheniya obratnoj transkripcii v CD4 limfocite virusnyj genom predstavlen nevstroennoj DNK Dlya vstraivaniya virusnoj DNK v genom kletki hozyaina i dlya obrazovaniya novyh virusov neobhodima aktivaciya T limfocitov Aktivaciya CD4 limfocitov proishodit pri ih kontakte s antigenpredstavlyayushimi kletkami v limfoidnoj tkani Nalichie virusov na poverhnosti follikulyarnyh dendritnyh kletok i prisutstvie provospalitelnyh citokinov IL 1 IL 6 i FNOa sposobstvuyut razmnozheniyu VICh v inficirovannyh kletkah Imenno poetomu limfoidnaya tkan sluzhit samoj blagopriyatnoj sredoj dlya replikacii VICh Sintezirovannaya virusnaya DNK transportiruetsya vnutr yadra kletki v sostave pre integracionnogo kompleksa v kotoryj takzhe vhodyat belki VICh p17 MA Nef i integraza Dalee virusnaya DNK vstraivaetsya v hromosomu aktivirovannogo T limfocita pod dejstviem integrazy Neskolko preparatov ingibiruyushih integrazu shiroko ispolzuyutsya v sovremennoj kompleksnoj antiretrovirusnoj terapii Virusnaya DNK vstroivshayasya v hromosomu kletki nazyvaetsya provirusom Transkripciya splajsing transport RNK iz yadra v citoplazmu i translyaciya V yadre kletochnaya RNK polimeraza sinteziruet predshestvennik virusnyh informacionnyh RNK mRNK dlina kotorogo ravna dline genomnoj RNK VICh 1 Etot predshestvennik mRNK podvergaetsya 5 koncevomu kepirovaniyu i 3 koncevomu poliadenilirovaniyu Krome togo predshestvennik mRNK podvergaetsya splajsingu v rezultate kotorogo obrazuyutsya bolee 40 raznyh mRNK kotorye mozhno razdelit na 3 klassa nesplajsirovannaya RNK dlinoj okolo 9 3 kb dalee ispolzuetsya v kachestve mRNK dlya sinteza belkov Gag i Gag Pol a takzhe v kachestve genomnoj RNK ne polnostyu splajsirovannye RNK razmerom okolo 4 kb ispolzuyutsya kak mRNK dlya sinteza belkov Vif Vpr Tat Vpu i Env polnostyu splajsirovannye RNK razmerom okolo 2 kb ispolzuyutsya kak mRNK dlya sinteza belkov Vpr Tat Rev i Nef Na rannej stadii ekspressii genov v otsutstvie belka Rev nesplajsirovannaya i ne polnostyu splajsirovannye RNK VICh 1 nestabilny i bystro razrushayutsya v yadre V to zhe vremya polnostyu splajsirovannye mRNK VICh 1 yavlyayutsya stabilnymi i transportiruyutsya iz yadra v citoplazmu V citoplazme s pomoshyu ribosom proishodit process translyacii biosintez belka iz aminokislot po zadannoj matrice na osnove geneticheskoj informacii soderzhashejsya v mRNK Sintezirovannyj v citoplazme belok Rev transportiruetsya v yadro gde svyazyvaetsya s oblastyu RRE nesplajsirovannoj i ne polnostyu splajsirovannyh RNK chto stabiliziruet eti RNK Krome togo Rev vzaimodejstvuet s kletochnym belkom CRM1 eksportin 1 i eto vzaimodejstvie stimuliruet transport nesplajsirovannoj i ne polnostyu splajsirovannyh RNK iz yadra v citoplazmu gde proishodit sintez zakodirovannyh v nih belkov Sborka i otpochkovyvanie virionov Genomnaya RNK virusa a takzhe virusnye belki transportiruyutsya k mestam sborki virionov k membrane Viriony pervonachalno formiruyutsya iz poliproteinov predshestvennikov strukturnyh belkov i fermentov i na etoj stadii ne yavlyayutsya infekcionnymi V hode sozrevaniya virusnoj chasticy virusnaya proteaza rassheplyaet belki predshestvenniki do funkcionalnyh komponentov Neskolko odobrennyh protivovirusnyh preparatov ingibiruyut rabotu proteazy i prepyatstvuyut formirovaniyu zrelyh virionov Novye virusnye chasticy otpochkovyvayutsya ot poverhnosti kletki zahvatyvaya chast eyo membrany i vyhodyat v krovyanoe ruslo a kletka hozyaina nesushaya receptor CD4 pogibaet Nedavnie issledovaniya pokazali chto process otpochkovyvaniya virionov mozhet byt bolee slozhnym chem schitalos ranee Tak bylo obnaruzheno chto blagodarya vzaimodejstviyu belka Gag s komponentami kletki viriony nakaplivayutsya v osobyh vnutrikletochnyh multivezikulyarnyh telcah kotorye obychno sluzhat dlya eksporta belkov Takim obrazom virusnye chasticy vysvobozhdayutsya iz kletki ekspluatiruya eyo sobstvennuyu sistemu transporta makromolekul Rasprostranenie po organizmu Tolko chto vydelivshijsya iz zarazhyonnogo limfocita virion VICh v plazme krovi zhivyot v srednem okolo 8 chasov Prodolzhitelnost poluzhizni vremya za kotoroe pogibaet 50 virionov VICh v plazme krovi sostavlyaet primerno 6 chasov V ostalnyh sredah prodolzhitelnost poluzhizni virionov VICh na poryadki menshe V period ostroj fazy VICh infekcii otsutstvie specificheskogo immunnogo otveta pozvolyaet virusu aktivno replicirovatsya i dostigat vysokih koncentracij v krovi Virus zaselyaet organy limfaticheskoj sistemy CD4 limfocity makrofagi a takzhe drugie kletki lyogkih kletki Langergansa follikulyarnye dendritnye kletki limfaticheskih uzlov kletki oligodendroglii i astrocity mozga i epitelialnye kletki kishki V limfoidnoj tkani VICh razmnozhaetsya na protyazhenii vsego zabolevaniya porazhaya makrofagi aktivirovannye i pokoyashiesya CD4 limfocity i follikulyarnye dendritnye kletki Kolichestvo kletok soderzhashih provirusnuyu DNK v limfoidnoj tkani v 5 10 raz vyshe chem sredi kletok krovi a replikaciya VICh v limfoidnoj tkani na 1 2 poryadka vyshe chem v krovi Osnovnym kletochnym rezervuarom VICh yavlyayutsya CD4 T limfocity immunologicheskoj pamyati Dlya aktivacii CD8 limfocitov i obrazovaniya antigen specificheskih citotoksicheskih T limfocitov neobhodima prezentaciya peptidnogo antigena v komplekse s chelovecheskim lejkocitarnym antigenom klassa I Dendritnye kletki neobhodimye dlya nachala pervichnyh antigen specifichnyh reakcij zahvatyvayut antigeny pererabatyvayut i perenosyat ih na svoyu poverhnost gde eti antigeny v komplekse s dopolnitelnymi stimuliruyushimi molekulami aktiviruyut T limfocity Zarazhyonnye kletki chasto ne vydelyayut dopolnitelnyh stimuliruyushih molekul i poetomu ne sposobny vyzvat aktivaciyu dostatochnogo chisla B i T limfocitov funkciya kotoryh zavisit ot dendritnyh kletok Na 2023 god VICh infekciya do sih por ostayotsya neizlechimym zabolevaniem tak kak genom virusa integriruetsya v hromosomy kletok i mozhet reaktivirovatsya dazhe posle kursa antiretrovirusnoj terapii V nastoyashee vremya idyot poisk bezopasnyh sposobov redaktirovaniya genoma cheloveka i isklyucheniya iz nego provirusnoj DNK V 2014 godu byl predlozhen metod udaleniya genoma VICh 1 iz zarazhyonnyh kletok pri pomoshi sistemy CRISPR Cas9 S pomoshyu etogo metoda issledovatelyam udalos vyrezat fragment provirusnoj DNK zaklyuchyonnyj mezhdu 5 i 3 koncevymi LTR oblastyami iz hromosom zarazhyonnyh kletok v kulture Krome togo etot metod okazalsya takzhe effektivnym dlya profilaktiki zarazheniya neinficirovannyh kletok Opisannyj podhod mozhet privesti k razrabotke sposoba polnogo izbavleniya ot VICh infekcii ProishozhdenieFilogeneticheskoe derevo virusov HIV virus immunodeficita cheloveka SIV virus immunodeficita obezyan Metodom molekulyarnoj filogenii pokazano chto virus immunodeficita cheloveka obrazovalsya v konce XIX ili v nachale XX veka skoree vsego v 1920 h gg Oba tipa virusa immunodeficita cheloveka VICh 1 i VICh 2 voznikli v Zapadnoj i Centralnoj Afrike yuzhnee Sahary i peredalis ot obezyan k lyudyam VICh 1 voznik na yuge Kameruna v rezultate evolyucii endemichnogo virusa immunodeficita obezyan SIV cpz kotoryj zarazhaet chernomordyh shimpanze Pan troglodytes troglodytes VICh 1 kak polagayut pereshyol vidovoj barer po krajnej mere trizhdy i porodil tri gruppy virusov M N i O VICh 2 voznik na territorii Zapadnoj Afriki ot yuzhnogo Senegala do zapada Berega Slonovoj Kosti v rezultate evolyucii virusa immunodeficita obezyan SIV smm kotoryj zarazhaet tyomno korichnevyh mangabeev Cercocebus atys predstavitelya martyshkoobraznyh uzkonosyh obezyan Sushestvuet dokazatelstvo togo chto ohotniki na dikih zhivotnyh obezyan ili postavshiki myasa v Zapadnoj i Centralnoj Afrike podvergayutsya zarazheniyu virusom immunodeficita obezyan prichyom veroyatnost zarazheniya korreliruet s chastotoj vzaimodejstviya s obezyanami i ih myasom Odnako virus immunodeficita obezyan slabyj virus i kak pravilo podavlyaetsya immunnoj sistemoj cheloveka v techenie nedeli posle zarazheniya Schitaetsya chto neobhodimo neskolko peredach virusa ot cheloveka k cheloveku v bystroj posledovatelnosti chtoby virusu hvatilo vremeni mutirovat v VICh Hotya peredacha virusa immunodeficita obezyan ot cheloveka k cheloveku proishodit redko opredelyonnye socialnye faktory mogut sushestvenno vliyat na chastotu zarazhenij Predpolagayut chto usloviya dlya rasprostraneniya virusa byli neblagopriyatny v Afrike do XX veka Sopostavlenie periodov uskorennoj evolyucii VICh s socio ekonomicheskimi izmeneniyami pozvolyaet delat predpolozheniya o prirode faktorov uskorivshih rasprostranenie VIO i VICh Geneticheskie issledovaniya pokazyvayut chto poslednij obshij predok VICh 1 gruppy M sushestvoval okolo 1910 goda Storonniki etoj daty svyazyvayut rasprostranenie VICh s razvitiem kolonializma v Afrike i rostom bolshih gorodov Eti faktory priveli k takim socialnym izmeneniyam v obshestve kak uvelichenie chastoty besporyadochnyh polovyh svyazej rasprostranenie prostitucii i zabolevanij peredayushihsya polovym putyom ZPPP ZPPP takie kak sifilis mogut soprovozhdatsya genitalnymi yazvami Issledovaniya pokazyvayut chto veroyatnost peredachi VICh vo vremya vaginalnogo polovogo akta dostatochno nizkaya pri obychnyh usloviyah mozhet byt uvelichena v desyatki esli ne v sotni raz esli odin iz partnyorov stradaet ot genitalnyh yazv O stepeni rasprostranyonnosti ZPPP v kolonialnyh gorodah v nachale 1900 h mozhno sudit po sleduyushim cifram v 1928 godu po menshej mere 45 zhitelnic vostochnogo Leopoldvilya nyne Kinshasa rannij centr rasprostraneniya VICh gruppy M byli prostituirovannymi zhenshinami a v 1933 godu okolo 15 vseh zhitelej etogo zhe goroda byli zarazheny odnoj iz form sifilisa Retrospektivnyj analiz pokazal chto nachalo epidemii VICh infekcii v Kinshase sovpalo s pikom epidemii genitalnyh yazv v seredine 1930 h godov Alternativnaya tochka zreniya glasit chto osnovnym faktorom sposobstvovavshim adaptacii VICh k lyudyam i ego rasprostraneniyu byla nebezopasnaya medicinskaya praktika v Afrike v gody posle Vtoroj mirovoj vojny takaya kak ispolzovanie nesterilnyh mnogorazovyh shpricev pri massovyh vakcinaciyah inekciyah antibiotikov i protivomalyarijnyh sredstv V rezultate retroanaliza obrazcov krovi vzyatyh posle Vtoroj mirovoj vojny zafiksirovan samyj rannij dokumentalnyj sluchaj nalichiya VICh v organizme cheloveka krov u kotorogo vzyali v 1959 godu Virus vozmozhno prisutstvoval v Soedinyonnyh Shtatah uzhe v 1966 godu no podavlyayushee bolshinstvo sluchaev zarazheniya VICh identificirovannyh za predelami tropicheskoj Afriki mozhno prosledit do odnogo neustanovlennogo cheloveka kotoryj zarazilsya VICh na Gaiti a zatem perenyos infekciyu v SShA okolo 1969 goda Mutaciya CCR5 D32Estestvennaya ustojchivost k VICh Sm takzhe CCR5 Mutaciya CCR5 D32 Opisany sluchai ustojchivosti lyudej k VICh Proniknovenie virusa v kletku immunnoj sistemy svyazano s ego vzaimodejstviem s poverhnostnym receptorom belkom CCR5 Deleciya uterya uchastka gena CCR5 delta32 privodit k nevospriimchivosti eyo nositelya k VICh Predpolagaetsya chto eta mutaciya voznikla primerno dve s polovinoj tysyachi let nazad i so vremenem rasprostranilas v Evrope Sejchas k VICh fakticheski ustojchiv v srednem 1 zhitelej Evropy 10 15 evropejcev imeyut chastichnuyu soprotivlyaemost k VICh 0 1 0 3 russkogo naseleniya pochti nevospriimchivy k VICh Uchyonye Liverpulskogo universiteta obyasnyayut rasprostranenie mutacii gena CCR5 tem chto ona usilivaet soprotivlyaemost k bubonnoj chume Epidemiya chyornoj smerti 1347 goda a v Skandinavii eshyo i 1711 goda sposobstvovala uvelicheniyu chastoty etogo genotipa v Evrope Mutaciya v gene CCR2 takzhe umenshaet shans proniknoveniya VICh v kletku i privodit k zaderzhke razvitiya SPIDa Sushestvuet nebolshoj procent VICh polozhitelnyh lyudej okolo 10 u kotoryh SPID ne razvivaetsya v techenie dolgogo vremeni Ih nazyvayut nonprogressorami nonprogressors Vazhnyj kletochnyj komponent zashity protiv VICh antivirusnyj belok APOBEC3G kotoryj vyzyvaet deaminirovanie DNK privodyashee k mutacionnym zamenam G na A v virusnoj DNK sinteziruemoj v hode obratnoj transkripcii APOBEC3G inaktiviruetsya belkom Vif VICh 1 kotoryj vyzyvaet ego ubikvitinilirovanie i degradaciyu Obnaruzheno chto odnim iz glavnyh elementov antivirusnoj zashity cheloveka i drugih primatov yavlyaetsya belok 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sleduyushem molekuly CD317 formiruyut parallelnyj gomodimer odin ili dva gomodimera svyazyvayutsya odnovremenno s odnim virionom i kletochnoj membranoj Pri etom s membranoj viriona vzaimodejstvuyut libo oba membrannyh yakorya transmembrannyj domen i GPI odnoj iz molekul CD317 libo odin iz nih Spektr aktivnosti CD317 vklyuchaet po krajnej mere chetyre semejstva virusov retrovirusy filovirusy arenavirusy i gerpesvirusy Aktivnost dannogo kletochnogo faktora ingibiruetsya belkami Vpu VICh 1 Env VICh 2 i SIV Nef SIV glikoproteinom obolochki virusa Ebola i belkom K5 gerpesvirusa sarkomy Kaposhi Obnaruzhen kofaktor belka CD317 kletochnyj belok VSA2 Breast cancer associated gene 2 Rabring7 ZNF364 RNF115 E3 ubikvitinligaza klassa RING BCA2 usilivaet internalizaciyu virionov VICh 1 privyazannyh belkom CD317 k poverhnosti kletki v CD63 vnutrikletochnye vezikuly s ih posleduyushim razrusheniem v lizosomah Sm takzheTimoti Rej Braun Berlinskij pacient pervyj chelovek kotoryj vylechilsya ot VICh 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