2.HIV Basic Principles English

8/8/2019 2.HIV Basic Principles English

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BASICS OF HIV


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What is HIV?

HIV is a RETROVIRUS. A Retrovirus is a ribonucleic acid

Deoxyribonucleic acid (DNA) beforereproducing/replicating.

It is the DNA gene that enables theVirus to replicate.


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What is HIV? Cont..d.

HIV belongs to the subclass of lentivirusesOR Slow viruses. Characterized by a longinterval between infection and

eve opmen o sease. Examples of Naturally Occurring Slow

viruses; Feline immune deficiency virus,

Simian immune deficiency viruses. Modelsfor Research.


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HIV types and sub-types

2 types of HIV: HIV-1 and HIV-2. Show40% to 60% amino acid homology.

-clades designated A to K(MClades) and O. M and O show 55-

70% similarity/homology. N clade is anew group recently reported.


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HIV-2

Human retrovirus. Mainly in W.Africa. Less transmissible(5-8fold less than HIV-1 in

early stage disease and in MTCT).

ower ra e o ec ne an seaseprogression.

20-30% of HIV-2 patients have negativeantibody tests.

Viral load tests are not generallyavailable.


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Structure of HIV


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Description-cont..d

VIRAL ENVELOPE- Outer coat of thevirus .Diameter of 1/10000 of amillimeter. S herical in sha e.

Composed of 2 layers of fat, calledlipid. Recent evidence suggests HIVmay Enter or exit cells through LIPIDRAFTS present on cell membrane.


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Description-cont..d

72 spikes on average made ofcomplex protein protrude from thevirion surface.This protein is called

ma e o a ap o ycoprotein 120 and a stem of GP41.

** Primary focus of VACCINE devt.


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Description-cont..d

Viral Core- Bullet shaped core calledCapsid made of 2000 copies of a proteincalled P24.

Capsid protects 2 single strands of HIVRNA,each with a copy of 9 genes. Gag,

Pol and Env gene encode for structural

proteins.E.g, Env gene encodes forGP160, that is broken down to GP120 andGP41.


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Description cont..d

6 regulatory genes control viralreplication. Include; Vif,Rev,Nef,Tat,Vpu,Vpr.

Other core protein include: p7- HIVnucleocapsid protein, and 3 enzymes-

Protease, Reverse transcriptase,

integrase. P17 matrix protein lies between the Core

and the envelope.


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Description of HIV structure


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Stages of HIV life cycles

1. Entry into the Cell. Involves 2 steps:a) Binding

- - .2. Reverse transcription- reverse

transcriptase converts HIV RNA to

Pro viral DNA.9 out of the 15 drugsact here.


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Stages of HIV lifecycle-cont..d

3. Integration- mediated by Integraseenzyme. Proviral DNA spliced intoHuman DNA.

4. Transcription-process of makingnew HIV RNA copies called

mRNA.mRNA will use the bodysprotein making machinery to makeviral proteins.


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Stages of HIV cycle-cont..d

5. Translation- Making of HIV structuralprotein using the hosts proteinmakin machiner .Processed HIV

mRNA copies acts as a template .Occurs in the cytoplasm.longchain proteins formed.

6. Assembly and budding. Cleavageof long chain proteins by protease.


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HIV Life Cycle


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Infected white blood cell


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Transmission of HIV

Unprotected sexual intercourse with aninfected person: HST, MSM, OS etc.

Contact with infected blood- needle stick

injury, sharing contaminated needles,blood transfusion.

Mother to child transmission; Before,

during birth and after birth through breastfeeding.


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Natural history of HIV

Viral transmission(2-3weeks)Acute retroviral syndrome

2-3weeks

Recovery and seroconversion

Asymptomatic chronic HIV infection

Av.8yearsSymptomatic HIV/AIDS

Av.1.3 years

Death


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Early Events in HIVprogression

Acute retroviral syndrome- occurs 2-3 weeks after acute HIV infection.70-80% suffer flu like s m toms.

Immune system fights back with killercells (CD8) and later B cells produceantibodies. This eventually leads to

CD4 recovery and reduction of HIVRNA to a low SET POINT.


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Later Course of Infection

Asymptomatic chronic stage. Averageof 8 years before progression to AIDS.

There is clinical latency while

Asymptomatic. Viral load determines rate of disease

progression-Velocity of progress.

CD4 counts-Where you are- Correlateswith risk of opportunistic infections.


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Advanced HIV/AIDSdisease stage

Defined by CD4 count less than200/mm3. Median survival 3.7years.

Characterized by opportunistic

infections, selectedtumors/cancers,wasting andneurological complications.

After AID defining complication,median survival is 1.3years.


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Correlation of complications with CD4

CD4 cell

count

Infection

complication

Non.infectious

complication

>500 Acute retroviralsyndrome

Candida vaginitis

PGL, myopathy,GBS,Aseptic meningitis

200-500 TB, Pneumonia,HZ,oralthrush,KS,OHL,cryptosporidiosis

Cervical cancer,anemia,lymphoma,mononeuronal simplex


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Correlation of complications with CD4counts

CD4 CellCount

Infectiouscomplication

Non-infectiouscomplication

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2.HIV Basic Principles English