Kwayar cutar kanjamau

Halittar kwayoyin halitta da sunadaran HIV (cutar cutar rashin lafiyar ɗan adam) sun kasance batun bincike mai zurfi tun lokacin da aka gano kwayar cutar a cikin shekarar 1983. "A cikin binciken da aka yi wa causative wakili, an yi imani da farko cewa kwayar cutar ta kasance nau'i na kwayar cutar sankarar jini ta T-cell na Human T-cell (HTLV), wanda aka sani a lokacin don rinjayar tsarin rigakafi na ɗan adam kuma ya haifar da wasu cututtukan sankarar bargo a baya.  jinsin kwayar cutar retrovirus daban-daban a cikin marasa lafiya da AIDS wanda daga baya aka sanya masa suna HIV."] Kowane virion ya ƙunshi ambulaf mai hoto mai hoto da matrix hade da ke rufe capsid, wanda da kansa ya ƙunshi kwafi biyu na kwayar halittar RNA mai ɗaci ɗaya da enzymes da yawa.  Gano kwayar cutar da kanta ya faru ne shekaru biyu bayan rahoton manyan cututtukan farko na cututtukan da ke da alaƙa da AIDS..

## Tsarinsa

Cikakken jerin kwayoyin halittar HIV-1, wanda aka core daga virions masu kamuwa da cuta, an warware shi zuwa ƙudurin nucleotide guda ɗaya. Kwayar halittar kwayar cutar kanjamau tana ƙunshe da ƙananan sunadarai na kwayar cuta, koyaushe tana kafa ƙungiyoyin hadin gwiwa tsakanin sunadarai ta kwayar cutar HIV da kuma tsakanin sunadarin HIV da sunadarin masu karɓar bakuncin, don mamaye sel masu karɓar baƙi da kuma sace kayan aikin su na ciki. Kwayar cutar kanjamau ta bambanta da tsarin daga sauran retroviruses. Kwayar cutar HIV tana da ~ 100 nm a diamita. Yankin da ya fi dacewa ya ƙunshi ainihin siffar ƙuƙwalwa wanda ya haɗa da kwafin biyu na (ma'anar) ssRNA genome, enzymes sun juya transcriptase, integrase da protease, wasu ƙananan sunadarai, da babban furotin. Kwayar cutar rigakafin mutum (HIV) tana ƙunshe da sunadarai 8 da ke taka muhimmiyar rawa a lokacin rayuwar HIV.&nbsp;

HIV-1 ya ƙunshi kwafin guda biyu na ba tare da alaƙa ba, ba tare da haɗuwa ba, RNA mai ma'ana guda ɗaya wanda aka kewaye shi da capsid mai ƙwayoyin cuta wanda ya ƙunshi furotin p24, wanda ya dace da Lentiviruses. RNAs guda biyu sau da yawa iri ɗaya ne, duk da haka ba su da 'yanci, amma suna samar da dimer a cikin virion. Dalilai da yawa game da dalilin da ya sa aka kunshe kwafin RNA guda biyu maimakon daya kawai an ba da shawarar, gami da yiwuwar haɗuwa da waɗannan fa'idodi: Ɗaya daga cikin fa'idori shine cewa kwafin RNA biyu suna da mahimmanci wajen ba da gudummawa ga sake haɗuwa da HIV-1, wanda ke faruwa yayin sake fasalin kwayar cuta, don haka ƙara bambancin kwayar halitta. Wani fa'ida shi ne cewa samun kwafin RNA guda biyu zai ba da damar sake fasalin transcriptase don canza samfurori lokacin da ya haɗu da raguwa a cikin kwayar cutar RNA, don haka ya kammala sake fasalin ba tare da asarar bayanan kwayar halitta ba. Duk da haka wani dalili shine cewa yanayin dimeric na kwayar cutar RNA na iya taka rawar gani a cikin kwayar cutar. Tsayar da kwafin guda biyu na RNA mai laushi a cikin virion amma samar da kwayar cutar DNA guda ɗaya ana kiranta pseudodiploidy .  Sashe na RNA yana da nucleotides 9749   kuma yana ɗauke da murfin 5 " (Gppp), wutsiya ta 3" poly (A), da kuma yawancin tsarin karatu (ORFs).  Ana sanya sunadarai na tsarin kwayar cuta ta hanyar ORFs masu tsawo, yayin da ƙananan ORFs ke tsara masu sarrafa tsarin rayuwar kwayar cutaa: haɗewa, haɗin membrane, maimaitawa, da taro.

RNA guda ɗaya yana daure sosai zuwa sunadaran p7 nucleocapsid, furotin taro na ƙarshen p6, da enzymes masu mahimmanci ga haɓakar virion, kamar jujjuya bayanan rubutu da haɗawa.  Lysine tRNA shine farkon abin da ke dogara da magnesium.  Nucleocapsid yana da alaƙa da RNA genomic (kwalli ɗaya a kowace hexamer) kuma yana kare RNA daga narkewa ta ƙwayoyin nucleases.  Hakanan an haɗa su a cikin kwayar cutar virion sune Vif, Vpr, Nef, da ƙwayoyin cuta.  [ana binciken hujja] [citation need] An samar da ambulaf na virion ta hanyar membrane plasma na asalin kwayar halitta, wanda ke tallafawa da matrix wanda ya ƙunshi furotin p17 na viral, yana tabbatar da amincin ƙwayar virion.  A saman virion za a iya samun iyakataccen adadin ambulan glycoprotein (Env) na HIV, trimer wanda heterodimers na gp120 da gp41 suka kafa.  Env yana da alhakin ɗaure mai karɓar mai karɓa na farko, CD4, da mai karɓar mai karɓar sa (yawanci CCR5 ko CXCR4), wanda ke haifar da shigarwar hoto ko bidiyo mai zagaya yanar gizo da sauri a cikin tantanin halitta.  

As the only proteins on the surface of the virus, the envelope glycoproteins (gp120 and gp41) are the major targets for HIV vaccine efforts. Over half of the mass of the trimeric envelope spike is N-linked glycans. The density is high as the glycans shield underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic reticulum and Golgi apparatus. The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on secreted or cell surface human glycoproteins. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to or, are adapted to cope with, these envelope glycans.

Tsarin kwayoyin ƙwayoyin cuta yanzu an ƙayyade shi ta hanyar X-ray crystallography  da cryo-electron microscopy.  Wadannan ci gaba a cikin ilmin halitta na tsari sun yiwu ne saboda ci gaban nau'ikan recombinant na ƙwayoyin cuta ta hanyar gabatar da haɗin disulphide da isoleucine zuwa maye gurbin proline a cikin gp41. Abin da ake kira SOSIP trimers ba wai kawai suna haifar da kaddarorin antigenic na ƙwayoyin cuta na asali ba har ma suna nuna irin wannan matakin glycans mara girma kamar yadda aka gabatar akan kwayar cutar ta asali. Recombinant trimeric viral spikes ne masu alkawarin rigakafin kamar yadda suke nuna ƙananan epitopes marasa tsaka-tsaki fiye da recombinant monomeric gp120 wanda ke aiki don murkushe amsawar rigakafi ga epitops da aka yi niyya.

## Tsarin kwayoyin halitta

HIV yana da manyan kwayoyin halitta da yawa da aka rubuta don sunadaran tsarin da ake samu a cikin duk retroviruses da kuma wasu kwayoyin halitta marasa tsari ("na'urorin haɗi") na musamman ga HIV.[1]  Kwayar cutar HIV ta ƙunshi kwayoyin halitta guda tara waɗanda ke ɓoye sunadaran ƙwayoyin cuta guda goma sha biyar.  Wadannan an haɗa su azaman polyproteins waɗanda ke samar da sunadaran don ciki na virion, wanda ake kira Gag, antigen na musamman;  enzymes na hoto (Pol, polymerase) ko glycoproteins na virion env (ambulaf).  Baya ga waɗannan, kwayar cutar HIV tana ƙididdige sunadaran sunadaran da ke da wasu ayyuka na tsari da na taimako suma.  HIV-1 yana da abubuwa masu mahimmanci guda biyu masu mahimmanci: Tat da Rev da wasu ƙananan sunadarai masu mahimmanci irin su Nef, Vpr, Vif da Vpu waɗanda ba su da mahimmanci don yin kwafi a cikin wasu kyallen takarda.  Ko da yake ana iya canza su ta hanyar maye gurbi, duk waɗannan kwayoyin halitta banda tev suna wanzuwa a cikin duk sanannun bambance-bambancen HIV;  duba canjin Halittu na

HIV yana amfani da tsarin da ya dace na bambancin RNA splicing don samun samfuran kwayoyin halitta daban-daban guda tara daga ƙasa da 10kb genome. HIV yana da 9.2kb unspliced genomic transcript wanda ke ƙunshe da gag da pol precursors; ƙunshe guda ɗaya, ƙunshe 4.5 kb don env, Vif, Vpr da Vpu da ƙunshe mai yawa, 2 kb mRNA ƙunshe don Tat, Rev da Nef.


Fayil:HIV-1_genome_image.svg|HIV-1
Fayil:Hiv-2_genome_image.svg|HIV-2


### Kwayoyin sunadarai na ƙwayoyin cuta

* *gag* (musamman antigen na rukuni) lambobin don pre-gag  wanda aka sarrafa ta hanyar protease na kwayar cuta yayin balaga zuwa MA (matrix protein, p17); CA (capsid protein, p24); SP1 (spacer peptide 1, p2); NC (nucleocapsid protein,p7); SP2 (spactor peptide 2, p1) da kuma P6 protein.
* *pol* lambobin don enzymes na kwayar cuta sun juya transcriptase (RT) da RNase H, integrase (IN), da kuma HIV protease (PR).  Ana buƙatar protease na HIV don raba pre-ga-garen Gag polyprotein don samar da sunadarai na tsari, ana buƙatar RT don fassara DNA daga samfurin RNA, kuma IN ya zama dole don haɗa DNA na kwayar cuta mai laushi biyu a cikin kwayar halitta.
* *env* (don "envelope") lambobin don gp160, wanda protease mai masaukin baki, furin, ya raba shi a cikin endoplasmic reticulum na tantanin halitta. Ayyukan bayan fassarar suna samar da glycoprotein na sama, gp120 ko SU, wanda ke haɗe da masu karɓar CD4 da ke kan lymphocytes, da gp41 ko TM, wanda ke sakawa a cikin ambulaf ɗin kwayar cuta don ba da damar haɗewa da haɗuwa da ƙwayoyin da aka yi niyya.

### Abubuwan da ke da mahimmanci

* *tat* (HIV trans-activator) plays an important role in regulating the reverse transcription of viral genome RNA, ensuring efficient synthesis of viral mRNAs and regulating the release of virions from infected cells. Tat is expressed as 72-amino acid one-exon Tat as well as the 86–101-amino-acid two-exon Tat, and plays an important role early in HIV infection. Tat (14–15kDa) binds to the bulged genomic RNA stem-loop secondary structure near the 5' LTR region forming the trans-activation response element (TAR).
* *rev* (regulator of expression of virion proteins): The Rev protein binds to the viral genome via an arginine-rich RNA-binding motif that also acts as a NLS (nuclear localization signals), required for the transport of Rev to the nucleus from cytosol during viral replication. Rev recognizes a complex stem-loop structure of the mRNA *env* located in the intron separating coding exon of Tat and Rev, known as the HIV Rev response element (RRE). Rev is important for the synthesis of major viral proteins and is hence essential for viral replication.&#x5B;**'&#x5D;</sup>

=== Protein masu sarrafawa ===

* ''vpr'' (protein na lentivirus R): Vpr wani nau'in furotin ne mai alaƙa da virion, nucleocytoplasmic shutting regulatory. An yi imanin cewa yana taka muhimmiyar rawa wajen kwayar cutar, musamman, shigo da nukiliya na hadaddun preintegration. Vpr kuma ya bayyana yana sa ƙwayoyin da ke karɓar bakuncin su dakatar da sake zagayowar sel ɗin su a matakin G2. Wannan kamawa yana kunna kayan gyaran DNA wanda zai iya ba da damar haɗa DNA na kwayar cuta. HIV-2 da SIV suna ƙunshe da ƙarin furotin mai alaƙa da Vpr wanda ake kira Vpx wanda ke aiki tare da Vpr.
* vif - Vif mai kiyayewa ne sosai, 23 kDa phosphoprotein yana da mahimmanci ga kamuwa da cutar HIV-1 virions dangane da nau'in tantanin halitta. An gano HIV-1 yana buƙatar Vif don hada ƙwayoyin cuta masu kamuwa a cikin lymphocytes, macrophages, da wasu layin sel na mutum. Ba ya bayyana yana buƙatar Vif don wannan tsari a cikin sel na HeLa ko sel na COS, da sauransu.
* nef - Nef, mummunan abu, shine N-terminal myristoylated membrane-associated phosphoprotein. Yana da hannu a cikin ayyuka da yawa yayin sake zagayowar kwayar cutar. An yi imanin cewa yana taka muhimmiyar rawa a cikin apoptosis na tantanin halitta da kara kamuwa da kwayar cuta.
* ''vpu'' (Virus protein U) - Vpu takamaiman ne ga HIV-1. Yana da aji na I oligomeric integral membrane phosphoprotein tare da ayyuka da yawa na halitta. Vpu yana da hannu a cikin lalacewar CD4 wanda ya shafi hanyar ubiquitin proteasome da kuma nasarar sakin virions daga sel masu kamuwa da cuta.  

=== Fusion sunadarai ===

* tev (TNV / p28tev): Wannan kwayar halitta tana nan ne kawai a cikin 'yan HIV-1 keɓaɓɓu. Yana da haɗuwa da ɓangarorin ''tat'', ''env'', da rev kwayoyin halitta, da lambobin furotin tare da wasu kaddarorin tat, amma kaɗan ko babu kaddarorin rev.

Don sake dubawa na sunadarai na fusion a cikin HIV-1, duba Langer da Sauter (2017). 

== Tsarin RNA na biyu ==
An gano abubuwa da yawa na tsarin tsarin sakandare da yawa a cikin kwayar cutar HIV RNA.  Tsarin RNA na kwayar cutar HIV yana daidaita ci gaban jujjuyawa.  [1] Tsarin 5'UTR ya ƙunshi jerin tsarin madauki-madauki da aka haɗa da ƙananan masu haɗin gwiwa] Waɗannan madaukai masu tushe (5'zuwa 3') sun haɗa da yanki na trans-activation (TAR), siginar polyadenylation na 5' [poly (A)], PBS, DIS, babban SD da ψ ψ hairpin tsarin da ke cikin 5' arshen kwayar cutar HIV (R)  gene.  Wani tsarin RNA wanda aka gano shine gag stem loop 3 (GSL3), wanda ake tunanin yana da hannu cikin marufi.  An gabatar da tsarin tsarin na biyu na RNA don shafar tsarin rayuwar kwayar cutar ta HIV ta hanyar canza aikin rigakafin cutar kanjamau da juyar da rubutun, kodayake ba duk abubuwan da aka gano ba ne aka sanya su aiki. 

Tsarin RNA na biyu wanda aka ƙaddara ta hanyar nazarin SHAPE ya nuna cewa yana ƙunshe da madauki uku kuma yana tsakanin protease na HIV da kwayoyin halitta na transcriptase. Wannan ''cis'' regulatory RNA an nuna cewa ana kiyaye shi a duk faɗin dangin HIV kuma ana zaton yana tasiri ga sake zagayowar rayuwar kwayar cuta.

== V3 madauki ==
Hanya ta uku mai canzawa **V3 madauki''' na V3 wani bangare ne ko yanki na Human Immunodeficiency Virus. Hanyar V3 na glycoprotein na envelope na viron, gp120, yana ba shi damar kamuwa da ƙwayoyin rigakafin ɗan adam ta hanyar ɗaurewa da mai karɓar cytokine a kan ƙwayoyin garkuwar ɗan adam, kamar ƙwayoyin CCR5 ko ƙwayoyin CXCR4, dangane da nau'in kwayar cutar kanjamau. Glycoprotein (Env) gp 120/41 yana da mahimmanci don shigar da HIV-1 cikin sel. Env yana aiki ne a matsayin kwayar halitta na magani da ke kula da mutane da ke fama da cutar HIV-1, da kuma tushen rigakafin cutar kanjamau. Koyaya, tsarin Env trimer mai aiki ya kasance mai rikitarwa.