Human Immunodeficiency

Virus: AIDS
INTRODUCTION
The first indication 1881, Newyork, USA
Two disease outbreaks Kaposis sarcoma & Pneumocystis
carnii
Aetiological agent isolated in 1983, Pasteur Institute,
Paris-Lymphadenopathy Assosciated Virus (LAV) lytic
lesions in peripheral lymphocytes.
1984, Robert Gallo reported, Retrovirus Human T cell
Lymphotropic Virus- III (HTLV-III)
Others reports AIDS Related Virus (ARV)
1986, International Committee on Virus nomenclature
generic name Human Immunodeficiency Virus (HIV)
 Human Immunodeficiency Virus (HIV)
Family : Retroviridae
Sub group: Lentivirus
Structure
Enveloped virus
90-120nm diameternucleoprotein core SS RNA & proteins
Reverse transcriptase enzyme
transcribed
Viral RNA SS DNA DS DNA(provirus)
Reverse transcriptase

integrates into host cell genome

Spikes surface component binds to CD4 receptor of host
Viral Genes and Antigens
Genome Structural gene, Non structural and regulatory gene.
Structural gene codes for structural protein
Gag gene determines core & shell of virus, expressed as
precursor protein, p55 3 component (p15,p18 & p24).
P24- core antigen, detected in serum early stage of HIV.
Env gene envelope, glycoprotein gp 120- surface spikes,
Gp 41- transmembrane anchoring protein.
Gp 120- ag, antibodies to gp 120 appear after infection
Pol gene polymerase reverse transcriptase & viral enzyme,
expressed as precursor protein, p100 3 components(p31,
p51 & p64)
Non structural and regulatory genes
tat gene transactivating factor, enhance viral protein
synthesis
art gene antirepressor transactivating gene promote viral
mRNA translation
2 LTR long terminal repeat promotor, enhancer and
integration signals
3 orf open reading frame reduce viral replication
(regulatory)
sor short open reading frame- gencodes poor immunogenic
protein
Antigenic variation
Variation among core & envelope antigens
2 antigenic types HIV 1 & HIV 2
Cell Tropism
CD4 antigen receptor for surface spike protein of HIV
HIV infect all cells bearing CD4 like
T4 (helper/inducer) lymphocytes
B lymphocytes 5-10%
Monocytes & macrophages 10-20% (alveolar
macrophages, langerhans cells in dermis, Glial cells and
microglia in CNS)
RESISTANCE
Not a hardy virus, thermolabile
Inactivated in 30 minutes at 56C
Susceptible to common disinfectants 70% ethanol, 35%
isopropyl alcohol, 5% lsol, 2.5% tween 20
Detergents and hot water
0.2% sodium hypochlorite2% solution of glutaraldehyde
Animal Immunodeficiency viruses
SAIDS Simian AIDS
Simian Immunodeficiency Virus or SIV
Acquired Immunodeficiency Syndrome
Pathogenesis
Transmission virus enters the blood or tissue and contact T4
lymphocytes
DS DNA transcript of virus integrates into infected host
genome cause latent infection.
Damage T4 lymphocytes, decrease in number.
Infected cell do not release IL-2, gamma interferon &
lymphokines dampening effect on CMI.
Helper T cell activity essential for optimal B cell function-
responding to thymus dependent antigens.
AIDS patient unable to respond to new antigens
Polyclonal activation of B lymphocytes hypergamma
globulinaemia
Levels of all immunoglobulins raised, especially Ig G, Ig
M & Ig A to irrelevant antigens and autoantibodies.
Responsible for type 3 hypersensitivity.
NK cells, Cytotoxic T lymphocytes, Monocyte &
Macrophage function affected.
Clinical manifestation not due to viral cytopathology, but
due to failure of immune response render patient
susceptible to opportunistic infection & malignancies
Exception dementia & degenerative neurological lesions
in AIDS due to direct effect of HIV on CNS.
Clinical Features
1.Acute HIV infection low grade fever, malaise, headache,
lymphadenopathy, rash etc
HIV antibodies negative, becomes positive on course.
Seroconversion illness
2.Asymptomatic infection infection lasting for months/years
shows HIV ab positive, minor opportunistic infections.
3. Persistent generalised Lymphadenopathy
4. AIDS related Complex(ARC)
5.AIDS- irreversible breakdown of immune defence mechanism
i. Respiratory dry cough, fever, pneumonia, Tb
ii. Gastrointestinal diarrhoea, abdominal pain, oesophageal
candidiasis, opportunistic infection Salmonella,
cryptosporidium, salmonella, mycobacteria, amoeba giardia
iii. CNS lymphoma of CNS, infection by herpes simplex, papova
virus, mycobacteria, aspergillus, candida
iv. Malignancies- Kaposis sarcoma
v. Cutaneous herpes lesion, candidiasis, xeroderma, impetigo,
molluscum contagiosum
vi. Dementia-encephalopathy
vii. Pediatric AIDS
Lab Diagnosis
A. Immunological test total leucocyte & lymphocyte count, T
cell subset assay, platelet count, Raised Ig G and A levels.
B. Demonstration of HIV antigen p24
C. Demonstration of antibodies Ig M and Ig G
D. Virus isolation co cultivation of patients lymphocytes with
uninfected lymphocytes in presence of IL-2
Serological test for anti HIV two types
Screening and Confirmatory
Screening
ELISA Direct Solid Phase ELISA
Ag from HIV grown in T lymphocyte cell line
Coated on microtitre plate
Test serum added, if ab present binds to ag
After washing anti human Ig linked to suitable enzyme
added
Followed by colour forming substrate
Positive serum contains anti HIV ab color formed read
spectrophotometrically
Confirmatory test
Western blot
HIV protein separated based on molecular weight by PAGE
Blotted on to strips of nitro cellulose membrane
Strips react with test sera and with enzyme conjugated anti
human globulin
Suitable substrate added
Produce color band where specific antibody reacted with
separated viral protein
Epidemiology
Sexually transmitted homosexuals
Blood and blood products
Mother to baby
Treatment
Treatment & prophylaxis of infection & tumours
General management
Immunorestorative measure administration of
IL-2, thymic factors, leucocyte transfusion & bone
marrow transplantation
Specific anti HIV agents alpha interferon, ribavirin,
suramin, foscarnet, Zidovudine (Azidothymidine, AZT)