3. HIV enfeksiyonu
Human immunodeficiency virus (HIV) tarafından sebep
olunan ilerledikçe immün sistemi yıkan bir hastalıktır
Akut HIV enfeksiyonu (bir kaç haftada sonlanır)
Asemptomatik HIV enfeksiyonu (10 yıl)
Erken semptomatik HIV enfeksiyonu
AIDS
11/02/14
3
4. Retroviruslar
Çift zincirli RNA virüsü
Lentivirus
HIV-1
HIV-2
Simian IDV
Onkovirus
Spumavirus
HTLV-1
Doğada yaygın
HTLV-II
patojenite?
Felin leukemia virus
Bovin leukemia virus
ENV ve GAG genlerine göre A-J’ye kadar 10 farklı türü vardır
Retrovirüsler viral RNA’nın reverz transkriptazını kullanarak lineer çift
zincirli DNA’ya döner ve konak genomuna integre olur.
11/02/14
4
10. HIV enfeksiyonu örnekleri
1959’da Kongo’dan erişkin erkekten alınan
serumda elde edildi.
1960’da Kongo’dan erişkin kadının lenf
bezinden saptandı.
1969’da St. Louis’de ölen bir Amerikalı
delikanlının (teeneger) doku örneğinde
1976’da ölen bir denizcinin doku örneklerinde
HIV saptandı
Zhu, T et. al (1998, 5th February) ' An African HIV-1 Sequence from 1959 and Implications for the Origin of the Epidemic ' Nature, 391
Worobey, M et. al (2008, 2nd October) ' Direct Evidence of Extensive Diversity of HIV-1 in Kinshasa by 1960 ' Nature, 455(7213)
Kolata, G (1987, 28th October) ' Boy's 1969 death suggests AIDS invaded U.S. several times ' New York Times
11/02/14
10
Frøland, SS et. al (1988, 11th June) ' HIV-1 infection in Norwegian family before 1970 ' The Lancet 331(8598)
11. EPİDEMİYOLOJİ
İlk kez 1981 yılında ABD de tanımlanmıştır
‘Akkiz immünyetmezlik sendromu’ adı verilmiştir
Etken virus 1983 yılında izole edilmiştir
11/02/14
11
14. Thelper lenfositler
B ve T sitotoksik lenfositlerinin aktivitelerini
şiddetlendirirler.
Çeşitli sitokinler salgılayarak
− T hücresi,
− monosit-makrofaj
güçlenmelerini sağlarlar.
Bu özellikleri ile Th lenfosit immün sitemin
orkestra şefi durumundadır.
11/02/14
14
16. Vücut sıvılarında HIV
Vücut sıvılarının 1ml’sinde ortalama HİV partikül sayısı
Kan
18,000
Semen
11,000
11/02/14
Vajinal
sıvı
7,000
Amniyotik
sıvı
4,000
Tükürük
1
16
17. BULAŞ YOLLARI
Cinsel yolla bulaş
− En önemli bulaş yoludur
− Bulaş için HIV pozitif kişiyle yapılan tek bir
cinsel temas yeterlidir
− Korunmasız cinsel temasta; virusun enfekte
erkekten kadına bulaş riski, enfekte kadından
erkeğe bulaş riskinden fazladır
11/02/14
17
20. Cinsel yolla bulaş riski
Sünnet (%50-60)
Kondom kullanımı
Tek eşlilik
11/02/14
HIV RNA
Genital ülser
Kanama
Birden çok cinsel eş
CYBH (üretrit, gonore)
20
21. Kan ve kan ürünleri ile bulaş
− HIV yönünden tarama yapılmaya (1985)
başlandığından beri bu yolla bulaş azalmıştır
Kan ve KÜ transfüzyonu
Organ transplantasyonu
Kornea ve işlenmiş dokularla
Bulaş riski yok
Yıl
Risk
1996
p24 antijeni
1/200.000-1/ 2.000.000
2002
11/02/14
Test
Nukleik asit testleri (12 gün) 1/ 2.135.000
21
22. Kan ve kan ürünleri ile bulaş
− Hepatit B İg
− İmmün serum globulin
− Rh İg
− Hepatit B aşısı
11/02/14
Bulaştırmaz
22
23. Damar içi madde kullanımı
İlişkili faktörler
− Enjektör ve diğer
aletlerle bulaş
Damar içi madde
kullananlar
İğne paylaşma sıklığı
Paylaşılan kişi sayısı
Enjeksiyon sayısı
Bölgedeki HIV sıklığı
Kokain enjeksiyonu daha riskli bulunmuş
11/02/14
23
24. Anneden bebeğe bulaş
Perinatal risk
%13-40
− Gebelik süresince
%30-50 doğumda +
− Doğum sırasında (%40)
− Postpartum dönemde
emzirmekle
%14-29
11/02/14
Preterm doğum
Uzamış membran
rüptürü (>4 saat)
Madde kullanımı
Antenatal düşük
CD4+ sayısı
Düşük doğum ağırlığı
24
25. Bebekte tanı
0-6 ayda PCR ve virüs kültürü (%50 tanı
koyar)
Anti-HIV ab 12-18 ay +
HIV-spesifik IgA (duyarlılığı düşük)
11/02/14
25
26. Sağlık bakımında HIV bulaşı
− Sağlık personeline bulaş
İğne,enjektör batması ile (risk %0.2-0.5)
Kanlı vücut sıvıları ile mukozal temasla (risk <%0.1)
− Sağlık personelinden hastaya
− 53 HIV’li çalışanın 2’sinin hastalarında +
Dişçi ve ortopedist
− Hastadan hastaya
− Malzemelerin tekrar kullanılması
− İlaçların çoklu kullanımı
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26
27. Bulaşın diğer yolları
Tükrükle ve ısırıkla bulaş nadirdir (kan
yoksa)
− HIV inhibitör etkisi
11/02/14
27
28. HIV enfeksiyonu ve antikor cevabı
---Başlangıç dönemi------------------Ara veya Latent Dönem------------Grip benzeri semptomlar
veya
Semptomsuz
Semptomsuz
---Hastalık Dönemi--
AIDS
----
Enfeksiyon
Virus
Antibody
---11/02/14
<
6 m ont h
~ Years
~ Years
~ Years
28
~ Years
29. TANI
FDA 2002
PCR
10-12 gün
P24 antijeni (combo test) 28 gün
16 gün
Anti HIV (3.kuşak ELISA) 3 ay (%97)
22 gün
Yeniler
*HIV-1 p17 IgM
7 gün
PEP almak, HCV koenfeksiyonu, agamaglobulinemi
Antikor yanıtının gecikmesine sebep olabilir
*Hashida S, et al. Clin Diagn Lab Immunol.2000; 7:872
11/02/14
29
30. HIV-enfekte erişkinlerde CDC sınıflaması
CD4 hücre sayısı
kategorileri
Klinik Kategori
: PGL = persistan generalize lenfadenopati
A
B*
C#
Asemptomatik, Akut Semptomatik, A AIDS-indikatör
HIV veya PGL
veya C dışı
durumlar
(1) ≥500 /µL
A1
B1
C1
(2) 200-499 /µL
A2
B2
C2
(3) <200 /µL
A3
B3
C3
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30
31. Kategori B Semptomatik durumlar
1. Bacillary angiomatosis
2. Orofaringeal kandidioz (thrush)
3. Vulvovaginal kandidoz, persistan veya rezistan
4. Pelvik inflammatuvar hastalık (PID)
5. Servikal displazi (orta, ağır)/servikal karsinoma in situ
6. Oral hairy lökoplaki,
7. Herpes zoster (shingles),en az bir dermatomu tutan veya ≥2 epizod
8. Idiopatik trombositopenik purpura
9. Konstitusyonel semptomlar (ateş>38.5ºC) ishal >1 ay
10. Periferik nöropati
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31
32. #
Kategori C AIDS-indikatör durumlar
Rekürren bakteriyel pnçmoni (12 ayda ≥2 epizod)
Bronş, trakea, akciğer kandidozu
Özefageal kandidoz
Servikal karsinoma, invaziv,
dissemine veya extrapulmoner koksidiyomikoz
extrapulmoner kriptokokkoz
Kronik intestinal kriptosporidyaz (>1 ay)
Cytomegalovirus hastalığı (KC, dalak ve LN dışı)
HIV-ensefalopatisi
Herpes simplex: kronik ülserler >1 ay, bronşit, pnömoni, özefajit
Histoplasmoz, disseminated or extrapulmonary
Izosporiyaz, kronick intestinal (>1 ay)
Kaposi sarkomu
Lenfoma, Burkitt, immunoblastik, primer santral sinir sistemi
Mycobacterium avium complex (MAC) veya Mycobacterium kansasii, dissemine veya ekstrapulmoner
Mycobacterium tuberculosis, pulmoner veya ekstrapulmoner
Mycobacterium, diğer türler, dissemine veya ekstrapulmoner
Pneumocystis jiroveci pnömonisi (PCP)
Progressif multifokal lökoensefalopati (PML)
Salmonella septisemi, rekürren
Beyin toxoplasmozu
Wasting sendromu (İstemeden kilo kaybı>%10) associated with either chronic diarrhea (hergün≥2
dışkılama ≥1 ay), kroniik yorgunluk, ateş ≥1 ay
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32
45. Tedavi
KLİNİK
KATEGORİ
CD4 HÜCRE
SAYISI
DHHS rehberi
IAS rehberi
(U.S)
BASHH
rehberi
Semptomatik
hasta
Herhangi bir
değer
Önerilir
Önerilir
Önerilir
Asemptomatik <350/mm3
hasta
Önerilir
Önerilir
Önerilir
Asemptomatik 350-500/mm3
hasta
Önerilir
Önerilir
Önerilir
Asemptomatik >500/mm3
hasta
Düşünülmeliopsiyonel
Düşünülmeli
Belli
durumlarda
öner
DHHS: Department of Health and Human Services (U.S)
BASHH: British association for sexual health and HIV
11/02/14
45
46. CD4 sayısından bağımsız tedavi
başlanmalı
Hastalığı hızlı ilerleme riski olanlar
− CD4 T hücrelerinin sayısında hızlı azalma (>100/mm3/yıl)
Viral yük >100 000 kopya/ml
>50 yaş
Kronik hepatit B veya hepatit C varlığı*
HIV ile ilişkili böbrek hastalığı
Yüksek kardiyovasküler risk
Fırsatçı hastalık varlığı
Gebelik
Malignite varlığı
Serolojik açıdan uyumsuz eş
11/02/14
46
50. KORUNMA
Cinsel yolla bulaşa karşı korunma
− Genital ve oral mukoza membranlarının cinsel ilişki
sırasında kan,semen,vajinal ve servikal
sekresyonlarla temasının azaltılması
− Kondom kullanımının teşvik edilmesi ve
yaygınlaştırılması
− Cinsel yolla bulaşan diğer hastalıkların tedavisi
− Güvenli cinsel temasın yaygınlaştırılması (tek eşli
cinsel yaşam veya uygun ve güvenli cinsel eş seçimi)
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50
51. Cinsel yolla bulaşa karşı korunma
•Erkek kondomunun
koruyuculuğu %60-96
•Kadın kondomu
kullanımı (%11-26
yetersiz)
11/02/14
51
52. Cinsel yolla bulaşa karşı korunma
Spermisit (nonoxinol 9) kullanımı HIV
bulaşını artırır
Mikrobisit (polinaftalen sülfonat gel (PRO2000) HIV sıklığını kısmen azalttı
11/02/14
52
53. Kan ve kan ürünleriyle bulaşa karşı
korunma
− Antikor testleri bulunduğundan beri bu yolla
bulaş azalmıştır
− Damar içi madde kullananlarda
− Bu alışkanlığın önlenmesi ve tedavi edilmesi
− Ortak enjektör kullanım risklerinin anlatılması
− Steril enjektör kullanımının sağlanması
− Eğitim
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53
54. Anneden bebeğe geçişe karşı korunma
− HIV pozitif kadına doğum kontrol yöntemleri
öğretilmelidir
− Hamile kalan HIV pozitif kadına erken dönemde kürtaj
yapılmalıdır
− Bebeği doğurmakta ısrarlı ise gebeliğin son
trimestırında anneye, doğumdan sonra da bebeğe
antiretroviral tedavi başlanmalıdır
− Elektif sezaryan uygulanırsa bebeğe HIV geçişi 4-5
kat azalır
− Virusun anne sütü ile geçişi gösterildiğinden emzirme
önerilmez
11/02/14
54
Simian virüs HIV1in prokürsörüdür. Retrovirüsler viral RNA’nın reverz transkriptazını kullanarak lineer çift zincirli DNA’ya döner ve konak genomuna integre olur. Pariste bir hastanın LN’da izole edildi.
HIV-2 birçok maymun türünü enfekte edebilir.
Once HIV comes into contact with a T-cell, it must attach itself to the cell so that it can fuse with the cell and inject its genetic material (a blueprint for making more HIV) into it. Attachment is a specific binding between proteins on the surface of the virus and proteins that serve as receptors on the surface of the T-cell. Normally, these receptors help the cell communicate with other cells. Two receptors in particular, CD4 and a beta-chemokine receptor (either CCR5 or CXCR4), are used by HIV to latch onto the cell. On the surface of the viral envelope, two sets of proteins (also known as antireceptors) called gp120 and gp41 attach to CD4 and CCR5/CXCR4.
Drugs called attachment or entry inhibitors are currently being studied in clinical trials. These drugs block the interaction between the cellular receptors and the antireceptor on the virus by binding to or altering the receptor sites. Scientists have found that people who naturally lack these cellular receptors because of a genetic mutation, or those who have them blocked by natural chemokines (chemical messengers), may not get infected as readily with HIV or may progress more slowly to AIDS. Scientists are also examining vaccines that may help the body block these receptors.
After attachment is completed, viral penetration occurs. Penetration allows the nucleocapsid -- the genetic core -- of the virus to be injected directly into the cell's cytoplasm. gp120 actually contains three sugar-coated proteins (glycoproteins) and, once gp120 attaches itself to CD4, these three proteins spread apart. This allows the gp41 protein, which is normally hidden by the gp120 proteins, to become exposed and bind to the chemokine receptor. Once this has occurred, the viral envelope and the cell membrane are brought into direct contact and essentially melt into each other.
Drugs called fusion inhibitors prevent the binding of gp41 and the chemokine receptor. T-20 (enfuvirtide, Fuzeon), an experimental fusion inhibitor that is nearing FDA approval, binds to a portion of gp41, preventing it from binding to the chemokine receptor.
Once HIV has penetrated the cell membrane, it is ready to release its genetic information (RNA) into the cell. The viral RNA is protected in the nucleocapsid. The nucleocapsid needs to be partially dissolved so that the virus's RNA can be converted into DNA, a necessary step if HIV's genetic material is to be incorporated into the T-cell's genetic core.
The process by which HIV's RNA is converted to DNA is called reverse transcription. This transcription process happens in almost every human cell, but in the opposite direction -- from DNA to RNA. DNA from the cell nucleus is transcribed into messenger RNA, which then directs the cell's various metabolic functions needed to do its job in the body. HIV uses an enzyme called reverse transcriptase to accomplish this transcription. The single-stranded viral RNA is transcribed into a double strand of DNA, which contains the instructions HIV needs to hijack a T-cell's genetic machinery in order to reproduce itself. Reverse transcriptase uses nucleotides -- building blocks of DNA -- from the cell cytoplasm to make this process possible.
Drugs called reverse transcriptase inhibitors block HIV's reverse transcriptase from using these nucleotides. Nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) -- such as Zerit, Epivir, and Viread -- contain faulty imitations of the nucleotides found in a T-cell's cytoplasm. Instead of incorporating a nucleotide into the growing chain of DNA, the imitation building blocks in NRTIs are inserted, which prevents the double strand of DNA from becoming fully formed. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) -- such as Viramune and Sustiva -- block reverse transcription by attaching to the enzyme in a way that prevents it from functioning.
If HIV succeeds in translating its instructions from RNA to DNA, HIV must then insert its DNA (also called the preintegration complex) into the cell's DNA. This process is called integration. In most human cells, there is a structure called the cell nucleus, where the cell's DNA is stored. In order for integration to occur, the newly translated DNA must be transported across the nuclear membrane into the nucleus.
Although the exact mechanism that HIV uses to transport its genetic cargo into the cell nucleus is still unclear, viral protein R (VPR), which is carried by HIV, may facilitate the movement of the preintegration complex to the nucleus. Once the viral RNA has successfully bridged the nuclear membrane and been escorted to the nucleus, HIV uses an enzyme called integrase to insert HIV's double-stranded DNA into the cell's existing DNA.
Drugs that inhibit the HIV preintegration complex from traveling to the nucleus -- integrase inhibitors -- are currently in early clinical trials.
After successful integration of the viral DNA, the host cell is now latently infected with HIV. This viral DNA is referred to as provirus. The HIV provirus now awaits activation. When the immune cell becomes activated, this latent provirus awakens and instructs the cellular machinery to produce the necessary components of HIV, like plastic pieces of a model airplane. From the viral DNA, two strands of RNA are constructed and transported out of the nucleus. One strand is translated into subunits of HIV such as protease, reverse transcriptase, integrase, and structural proteins. The other strand becomes the genetic material for the new viruses. Compounds that inhibit or alter viral RNA have been identified as potential antiviral agents.
Once the various viral subunits have been produced and processed, they must be separated for the final assembly into new virus. This separation, or cleavage, is accomplished by the viral protease enzyme.
Drugs called protease inhibitors -- such as Kaletra, Crixivan, and Viracept -- bind to the protease enzyme and prevent it from separating, or cleaving, the subunits.
If cleavage is successfully completed, the HIV subunits combine to make up the content of the new virons. In the next step of the viral life cycle, the structural subunits of HIV mesh with the cell's membrane and begin to deform a section of the membrane. This allows the nucleocapsid to take shape and viral RNA is wound tightly to fit inside the nucleocapsid. Researchers are looking at drugs called zinc finger inhibitors, which interfere with the packaging of the viral RNA into the nucleocapsid.
The final step of the viral life cycle is called budding. In this process, the genetic material enclosed in the nucleocapsid merges with the deformed cell membrane to form the new viral envelope. With its genetic material tucked away in its nucleocapsid and a new outer coat made from the host cell's membrane, the newly formed HIV pinches off and enters into circulation, ready to start the whole process again.
During HIV's life cycle, the T-cell, known as the host cell, is altered and perhaps damaged, causing the death of the cell. Scientists are not sure exactly how the cell dies but have come up with a number of scenarios. First, after the cell becomes infected with a virus or other pathogen, internal signals may tell it to commit suicide. This is known as apoptosis or programmed cell death -- a self-destruct program intended to kill the cell with the hopes of killing the virus as well. A second possible mechanism for the death of the cell is that, as thousands of HIV particles bud or escape from the cell, they severely damage the cell's membrane, resulting in the loss of the cell. Another possible cause for the cell's death is that other cells of the immune system, known as killer cells, recognize that the cell is infected and inject it with chemicals that destroy it.
Montaj
In February 1999 a group of researchers from the University of Alabama2 announced that they had found a type of SIVcpz that was almost identical to HIV-1. This particular strain was identified in a frozen sample taken from a captive member of the sub-group of chimpanzees known as Pan troglodytes troglodytes (P. t. troglodytes), which were once common in west-central Africa.
Hunter; The most commonly accepted theory is that of the 'hunter'. In this scenario, SIVcpz was transferred to humans as a result of chimps being killed and eaten or their blood getting into cuts or wounds on the hunter.
HIV can be transmitted from mother to infant during pregnancy, childbirth,
or breastfeeding.
Viral yük düşük olduğundan PCR – olabilir.
PEP almak, HCV koenfeksiyonu, agamaglobulinemi
Antikor yanıtının gecikmesine sebep olabilir
Once HIV comes into contact with a T-cell, it must attach itself to the cell so that it can fuse with the cell and inject its genetic material (a blueprint for making more HIV) into it. Attachment is a specific binding between proteins on the surface of the virus and proteins that serve as receptors on the surface of the T-cell. Normally, these receptors help the cell communicate with other cells. Two receptors in particular, CD4 and a beta-chemokine receptor (either CCR5 or CXCR4), are used by HIV to latch onto the cell. On the surface of the viral envelope, two sets of proteins (also known as antireceptors) called gp120 and gp41 attach to CD4 and CCR5/CXCR4.
Drugs called attachment or entry inhibitors are currently being studied in clinical trials. These drugs block the interaction between the cellular receptors and the antireceptor on the virus by binding to or altering the receptor sites. Scientists have found that people who naturally lack these cellular receptors because of a genetic mutation, or those who have them blocked by natural chemokines (chemical messengers), may not get infected as readily with HIV or may progress more slowly to AIDS. Scientists are also examining vaccines that may help the body block these receptors.
After attachment is completed, viral penetration occurs. Penetration allows the nucleocapsid -- the genetic core -- of the virus to be injected directly into the cell's cytoplasm. gp120 actually contains three sugar-coated proteins (glycoproteins) and, once gp120 attaches itself to CD4, these three proteins spread apart. This allows the gp41 protein, which is normally hidden by the gp120 proteins, to become exposed and bind to the chemokine receptor. Once this has occurred, the viral envelope and the cell membrane are brought into direct contact and essentially melt into each other.
Drugs called fusion inhibitors prevent the binding of gp41 and the chemokine receptor. T-20 (enfuvirtide, Fuzeon), an experimental fusion inhibitor that is nearing FDA approval, binds to a portion of gp41, preventing it from binding to the chemokine receptor.
Once HIV has penetrated the cell membrane, it is ready to release its genetic information (RNA) into the cell. The viral RNA is protected in the nucleocapsid. The nucleocapsid needs to be partially dissolved so that the virus's RNA can be converted into DNA, a necessary step if HIV's genetic material is to be incorporated into the T-cell's genetic core.
The process by which HIV's RNA is converted to DNA is called reverse transcription. This transcription process happens in almost every human cell, but in the opposite direction -- from DNA to RNA. DNA from the cell nucleus is transcribed into messenger RNA, which then directs the cell's various metabolic functions needed to do its job in the body. HIV uses an enzyme called reverse transcriptase to accomplish this transcription. The single-stranded viral RNA is transcribed into a double strand of DNA, which contains the instructions HIV needs to hijack a T-cell's genetic machinery in order to reproduce itself. Reverse transcriptase uses nucleotides -- building blocks of DNA -- from the cell cytoplasm to make this process possible.
Drugs called reverse transcriptase inhibitors block HIV's reverse transcriptase from using these nucleotides. Nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) -- such as Zerit, Epivir, and Viread -- contain faulty imitations of the nucleotides found in a T-cell's cytoplasm. Instead of incorporating a nucleotide into the growing chain of DNA, the imitation building blocks in NRTIs are inserted, which prevents the double strand of DNA from becoming fully formed. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) -- such as Viramune and Sustiva -- block reverse transcription by attaching to the enzyme in a way that prevents it from functioning.
If HIV succeeds in translating its instructions from RNA to DNA, HIV must then insert its DNA (also called the preintegration complex) into the cell's DNA. This process is called integration. In most human cells, there is a structure called the cell nucleus, where the cell's DNA is stored. In order for integration to occur, the newly translated DNA must be transported across the nuclear membrane into the nucleus.
Although the exact mechanism that HIV uses to transport its genetic cargo into the cell nucleus is still unclear, viral protein R (VPR), which is carried by HIV, may facilitate the movement of the preintegration complex to the nucleus. Once the viral RNA has successfully bridged the nuclear membrane and been escorted to the nucleus, HIV uses an enzyme called integrase to insert HIV's double-stranded DNA into the cell's existing DNA.
Drugs that inhibit the HIV preintegration complex from traveling to the nucleus -- integrase inhibitors -- are currently in early clinical trials.
After successful integration of the viral DNA, the host cell is now latently infected with HIV. This viral DNA is referred to as provirus. The HIV provirus now awaits activation. When the immune cell becomes activated, this latent provirus awakens and instructs the cellular machinery to produce the necessary components of HIV, like plastic pieces of a model airplane. From the viral DNA, two strands of RNA are constructed and transported out of the nucleus. One strand is translated into subunits of HIV such as protease, reverse transcriptase, integrase, and structural proteins. The other strand becomes the genetic material for the new viruses. Compounds that inhibit or alter viral RNA have been identified as potential antiviral agents.
Once the various viral subunits have been produced and processed, they must be separated for the final assembly into new virus. This separation, or cleavage, is accomplished by the viral protease enzyme.
Drugs called protease inhibitors -- such as Kaletra, Crixivan, and Viracept -- bind to the protease enzyme and prevent it from separating, or cleaving, the subunits.
If cleavage is successfully completed, the HIV subunits combine to make up the content of the new virons. In the next step of the viral life cycle, the structural subunits of HIV mesh with the cell's membrane and begin to deform a section of the membrane. This allows the nucleocapsid to take shape and viral RNA is wound tightly to fit inside the nucleocapsid. Researchers are looking at drugs called zinc finger inhibitors, which interfere with the packaging of the viral RNA into the nucleocapsid.
The final step of the viral life cycle is called budding. In this process, the genetic material enclosed in the nucleocapsid merges with the deformed cell membrane to form the new viral envelope. With its genetic material tucked away in its nucleocapsid and a new outer coat made from the host cell's membrane, the newly formed HIV pinches off and enters into circulation, ready to start the whole process again.
During HIV's life cycle, the T-cell, known as the host cell, is altered and perhaps damaged, causing the death of the cell. Scientists are not sure exactly how the cell dies but have come up with a number of scenarios. First, after the cell becomes infected with a virus or other pathogen, internal signals may tell it to commit suicide. This is known as apoptosis or programmed cell death -- a self-destruct program intended to kill the cell with the hopes of killing the virus as well. A second possible mechanism for the death of the cell is that, as thousands of HIV particles bud or escape from the cell, they severely damage the cell's membrane, resulting in the loss of the cell. Another possible cause for the cell's death is that other cells of the immune system, known as killer cells, recognize that the cell is infected and inject it with chemicals that destroy it.
