HIV is a retro virus.containing RNA.

1. HIV
DR VARSHA SATWIK

2. RETROVIRUSE
S
• THEY POSSESS A UNIQUE ENZYME
CALLED REVERSE TRANSCRIPTASE THAT
DIRECTS THE SYNTHESIS OF DNA FROM
VIRAL RNA AFTER THEY INFECT THE HOST
CELL.
• TWO GENERA :
• Genus Lentivirus: Human Immunodeficiency
virus HIV 1 & 2
• Genus Delta retrovirus : Human T cell
lymphotropic virus HTLV1

3. • HIV
•HUMAN IMMUNODEFICIENCY VIRUS

4. • HIV IS ETIOLOGIC AGENT OF ACQUIRED IMMUNODEFICIENCY SYNDROME AIDS
• HISTORY:
• First case of AIDS described from New York USA in1981
• Followed by HIV1 isolation from Pasteur Institute Paris 1983
• Luc Montagnier & collegues 1983 isolated Retrovirus from West African patient
with generalized lymphadenopathy which is manifestation of AIDS & named it LAV
(Lymphadenopathy associated virus )
• 1984 National Institute Of Health USA isolated Retrovirus from AIDS patient &
called it HTLV III Human T Lymhocytic Virus III
• Other viruses isolated from AIDS patients were named ARV AIDS RELATED
VIRUSES
• All viruses were given a name HIV by International Committee on virus
nomenclature 1986

5. • MORPHOLOGY:
• Spherical Enveloped Virus 80 – 120 nm in size.
• Nucleocapsid : Outer icosahedral shell & an inner cone shaped core enclosing
ribonucleoproteins.
• Genome : is diploid composed of 2 identical single stranded +ve sense RNA
copies
• RNA is associated with REVERS TRANSCRIPTASE ENZYME.
• Envelope : Enveloped by lipid ,bilayer glycoprotein envelop
• 1.Derived from host cell membrane
• 2. 72 spikes projecting from surface formed of glycoprotein gp 120 & gp
41. Below viral envelope is a layer called matrix made up of p17
• 3. Spikes help in binding virus particle to CD4 receptors on cell surface.

6. STRUCTURE OF HIV

7. • VIRAL GENES
• 3 TYPES OF GENES in virus which encodes the structural proteins of virus.
• Genes encoding structural proteins are :
• 1. gag gene
• 2. env gene
• 3. pol gene
• 1.gag gene : encodes for the core proteins (i) determine core & shell of
virus (ii) expressed as precursor
protein p55. This is cleaved in 3 proteins p15, p18, p 24 (numericals are
their mass in kilodaltons) (iii) p18 makes viral shell p24 is principal core
protein.

8. • 2. env gene : encodes for the envelope proteins.
• Main envelope glycoprotein is gp 160 which is cleaved into gp 120
which forms surface spikes & gp 41 which is transmembrane pedicle protein.
• 3. pol gene : encodes for reverse transcriptase & other viral enzymes protease
,endonuclease & integrase. Expressed as p31 p51 & p66 proteins.
• NONSTRUCTURAL & REGULATORY GENES
• 1. tat : transactivating gene
• 2. nef : negative factor gene
• 3. rev : regulator of virus gene
• 4. viral infectivity factor gene
• 5. vpu : in HIV1 & vpx in HIV2
• 6. vpr : increases the transport of viral genome into nucleus & arrests host growth.
• 7. vpx : found in HIV2. Closely related to vpr
• 8. LTR : Long terminal repeat. Provide promotor,enhancer & integration signals.

9. • ANTIGENS:
• 1. ENVELOPE ANTIGEN : Spike ag gp 120
• Transmembrane pedicle protein gp 41
• 2. SHELL ANTIGEN: Nucleocapsid protein p18
• 3. CORE ANTIGEN : Principal core ag p24 . Other core ag p15,p55
• 4. POLYMERASE ANTIGEN : p31 p51,p66
• ANTIGENIC TYPES :
• HIV1 & HIV2 They are distinguished by differences in ab reactivity to envelope
glycoprotein.
• Antigenic variation : HIV is highly mutable virus. Antigenic variations occur
frequently with envelope proteins.

10. • HIV 1 : Strains classified in at least 10 subtypes based on sequence analysis of
their gag(group specific antigen ) & envelope genes. They are A to J
• HIV 2: less virulent than HIV1 .Largely confined to West Africa.
• VIABILITY : 1. Thermolabile- Gets inactivated in 10 min. x at 50 c & in seconds at
100 c
• 2. Room temp. – 20-25 c in dried blood may survive upto 7 days.
• 3. In lypholised blood products virus can be inactivated by heating at 68 c for 72
hours & in liquid plasma at 60 c for 10 hours.
• 4. Inactivates at extremes of pH 1 & 13
• 5.Inactivates in 10 min, by t/t with 50% ethanol 35% isopropanol & 0.3% Hydrogen
peroxide.
• 6. Bleaching powder or household bleach are effective for surface
decontamination.
• 7.For t/t of medical instruments contaminated with HIV 2% solution of

11. • REPLICATION
• 1. Adhesion
• 2.Penetration
• 3.Reverse transcription & integration
• 4.Transcription & translation
• 5.Assembly / Budding/ Maturation
• PATHOGENESIS
• 1.Receptor for the virus is CD4 antigen on the surface of cell.
• 2. Virus attaches to cells with help of envelope protein gp 120.
• gp 120 has special affinity for CD4 receptors.

12. 3. CD4 receptors are present on T lymphocytes. Other cells with CD4 receptors are B lymphocyte
,monocytes & macrophages. Glial cells & microglia in CNS & dendritic cells from tonsils are found
to be infected.
4 Infection is transmitted when virus enters blood or tissues .Virus can be isolated from blood,
lymphocytes, cell free plasma, semen, cervical secretions, saliva, tears, urine & breast milk.
5.Primary effect of HIV infection is damage to T4 lymphocyte. T4 cells decrease in numbers. T4: T8
(Helper : Suppressor) cell ratio is seen to be reversed which is a characteristic feature of HIV
infection. NK cells function is affected so phagocytic function is disturbed.
6. Imp. Feature of HIV inf. is polyclonal B cell activation which will result into
hypergammaglobulinemia esp. IgG & IgA. But these are useless antibodies & autoantibodies.
7. Cl.manif. of HIV infection is secondary due to failure of immune responses rather than primary
due to viral cytopathology.
8.Failure of immune response renders patient susceptible to opportunistic infection & malignancies.

13. • MODE OF TRANSMISSION
• 1.Sexual Transmission :
• Most common route of transmission is heterosexual route. Risk is greatest with
anal sex than vaginal sex because it more likely to rupture tissues of receptive
partner.
• 2. Perinatal transmission :
• Infected mother to fetus, infant during delivery & breast feeding.
• 3. Blood contact :
• Blood transfusion ,contaminated needles syringes, skin piercing , tattoing.
• INCUBATION PERIOD : FEW MONTHS TO SIX YEARS OR EVEN MORE

14. • CLINICAL FEATURES
• 1. INITIAL PHASE :
• Malaise , fever , myalgia, arthralgia, nausea , vomiting , sore throat & rashes
• Intense viremia for few weeks followed by appearance of antibodies seen between
2-12 weeks following infection.
• Period before antibodies are formed is known as WINDOW PERIOD ( sero negative
infective stage )
• 2 ASYMPTOMATIC PHASE :
• Patient shows no symptoms but antibodies are present
• Lasts for several months to year
• Slow progressive decline in CD4 cell count.

15. • 3. AIDS RELATED COMPLEX
• llness is caused by damage to immune system but no opportunistic infection seen
• Following signs are present :
• 1.Prolonged diarrhoea
• 2.Malaise , fatigue
• 3.Loss of body weight > 10%
• 4.Generalised lymphadenopathy & spleenomegaly
• 4. AIDS :
• End stage of HIV infection
• No. of opportunistic infection & malignancies occur.

16. • OPPORTUNISTIC INFECTION & MALIGNANCIES TYPICALLY ASSOCIATED WITH HIV INFECTION
• 1. PARASITIC : 1. Pneumocystis carinii pneumonia
• 2.Toxoplasmosis
• 3.Cryptosporidiosis
• 4. Isosporiasis
• 5. Generalised Strongyloidiosis
• 2. MYCOTIC : 1.Candidiasis
• 2.Cryptocosis
• 3. Asperigillosis
• 4. Histoplasmosis
• 3. BACTERIAL : 1. Mycobacterial infection TB & Non TB
• 2. Salmonellosis
• 3. Campylobacter inf.
• 4. Nocardia & Actinomycetes
• 5. Legionellosis
• 4.VIRAL : 1. CMV
• 2. Herpes Simplex
• 5. Malignancies : 1. Kaposis Sarcoma
• 2. Lymphoma Hodgkin & Non Hodgkin types

17. WHO DEFINITION OF AIDS
Atleast 2 major & 2 minor signs are present.
• Major Signs
• 1.Weight loss >10% of body weight
• 2.Chronic diarrhoea > 1 month
• 3.Prolonged fever > 1 month
• Minor Signs
• 1.Persistent cough > 1month
• 2.Generalised pruritic dermatitis
• 3.Herpetic simplex infection
• 4.Oropharyngeal candidiasis
• 5. Generalized lymphadenopathy

18. LABORATORY DIAGNOSIS
• 1. Demonstration of antibody to HIV :
• Antibodies appear in 2-12 weeks. If infection present then
• (i) IgM appears in 2-4 weeks & disappear in 8-10 weeks
• (ii) IgG antibodies is there throughout the period.
• Tests for detection of antibodies for HIV :
• (i) ELISA : Standard test for detection of HIV infection
• False +ve reactions seen in RA factor
• (ii) Indirect Immunofluroscence test
• (iii) Western Blot test CONFIRMATORY for HIV

19. • WESTERN BLOT TEST
• (a) Based on detecting antibodies to viral core protein & envelope protein
• (b) In this test HIV proteins are separated according to their electrophoretic mobility &
molecular weight by polyacrylamide gel electrophoresis.
• (c) After the proteins are separated these are blotted into strips of nitrocellulose paper.
These strips are made to react with test sera & then with enzyme conjugated antihuman
globulin.
• (d)It is made to react with a suitable substrate which produces color bands on the strips
where antibodies have reacted with antigens. The position of the color band indicate that
the antigen with which antibody has reacted.
• In HIV positive case bands will be seen with multiple proteins like gp 41, gp 160, gp 120,
p15, p 24.
•

20. HIV WESTERN BLOT TEST STRIP

21. • 2.Antigen demonstration
• Virus antigen p24 may be detected in blood after 2 weeks. Ag not detectable during
asymptomatic phase but titre rises as the clinical condition sets in.
• 3. PCR
• HIV –RNA assay by RT-PCR ( Reverse transcription polymerase chain reaction )
• 4. Ora Sure’s Ora Quick HIV antibody testing .False negative 8% of
133 tested.
• 5. Combination of Ag/Ab tests : 4th generation assay detects HIV as early as
2-6 weeks after infection.

22. • LABORATORY PARAMETERS :
• 1. Leucopenia
• 2.T4:T8 is reversed (T4 count <200/cumm)
• 3. Low Platelet count
• 4. Raised IgG & IgM level
• 5. Lymph node biopsy in lymphadenopathy shows changes.

23. EVOLUTION OF SEROLOGICAL MARKERS DURING HIV
INFECTION MARKERS
STATE OF INF. p24 Ag free anti HIV IgG
• Early inf. - -
• Acute +to - - to +
• (Seroconversion)
• Carrier - +
• (asymptomatic)
• PGL + +
• Persistent generalized lymphadenopathy
• AIDS +
Anti HIV IgM Western Blot pattern
• - -
• + Partial p24 & or gp 120
•
• - Full pattern
•
• - Loss of p24/p 55
• Absence of p24

24. • TREATMENT
• No specific t/t is available by now
• 1.Treat specifically for opportunistic infection
• 2.Immunorestortive therapy like administration of inter IL – 2 Bone marrow transplantation
• 3.Antiretroviral therapy : Zidovudine Zalcitabine Stavidine
• PROPHYLAXIS
• 1. Health education
• 2.Identification of source
• 3. Elimination of source