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Human Immunodeficiency Virus
BY:
MANISH DHAWAN
INTRODUCTION Family: Retroviridae Genus: Lentiviridae Disease that HIV causes, AIDS was first
reported in the U.S. in 1981 in L.A. and New York
Causative agent discovered and characterized by Luc Montagnier of France and Robert Gallo of the US in 1983-84.
Retrovirus having:
Reverse transcriptase
Antigenic strains : HIV-1 and HIV-2 HIV-1(virulent strain) is most prominent in
U.S., Canada and Europe HIV-2 (less virulent) common in certain
parts of West Africa, it is closely related to simian immunodeficiency virus (SIV) found in monkey
HIV-1 differs significantly from HIV-2/SIV.
structure Each virion expresses 72 glycoprotein projections composed of gp120 and gp41
The viral envelope derives from the host cell and contains some host-cell membrane proteins, including class I and class II MHC molecules
Within the envelope is the viral core, or nucleocapsid, which includes a layer of a protein called p17 and an inner layer of a protein called p24.
Genome consists of two copies of single-stranded RNA, which are associated with two molecules of reverse transcriptase (p64) and nucleoid proteins p10, a protease,
and p32, an integrase.
Electron micrograph of HIV virions magnified 200,000 times. The glycoprotein projections are faintly visible as “knobs” extending from the periphery of each virion.
Genome of HIV-1 Structural genes
gag :- Group specific antigen, pol :- Reverse transcriptase, Protease
and Integrase, env :- Envelope glycoprotein (gp).
Genes essential for viral replication:
tat :- activates transcription,
rev :- export of unspliced and singly spliced mRNAs from nucleus,
LTR sequence:- promoter and enhancer elements
Genes not essential for viral replication:-
vif :- promotes maturation and infectivity
nef (negative factor) :- Down-regulates Host-cell class I MHC and CD4
vpr , vpx and vpu
StabilityInactivation By :-
Heat a) Autoclave b) hot air oven Glutaraldehyde 2% Hypochlorite 10,000 ppm : 1 in 10 dilution of domestic
bleach Other disinfectants, including alcohols .
Survival of HIV :-
Virus may survive for up to 15 days at room temperature. At 37º C virus can survive for 10-15 days. Over 60º C virus is inactivated 100-fold each hour.
Viral Infection
M-tropic, binds to CD4 and CCR5 of macrophage
T-tropic viruses infect T cells by binding with CD4 and CXCR4.
Viral Replication
HIV infecting a T-lymphocyte
Destruction of T-cells
Pathogenesis :- Latency Period
Destruction of Immune System
HIV-Time Course
Acquired Immunodeficiency Syndrome
• Disease limits the body’s ability to fight infection due to markedly reduced helper T cells
• CD4 count drops below 200 person is considered to have advanced HIV disease
• If preventative medications not started the HIV infected person is now at risk for:– Pneumocystis carinii pneumonia (PCP)– cryptococcal meningitis– toxoplasmosis
NATURAL COURSE OF HIV/AIDS
Stage 1 - Primary
Short, flu-like illness - occurs one to six weeks after infection
Mild symptoms Infected person can
infect other people
Stage 2 - Asymptomatic Lasts for an average of ten years This stage is free from symptoms There may be swollen glands The level of HIV in the blood drops to low levels HIV antibodies are detectable in the blood
Stage 3 - Symptomatic
The immune system deteriorates Opportunistic infections and cancers start to
appear.
Stage 4 - HIV AIDS
The immune system weakens too much as CD4 cells decrease in number.
Opportunistic Infections associated with AIDS
CD4<500 Bacterial infections Tuberculosis (TB) Herpes Simplex Herpes Zoster Vaginal candidiasis Hairy leukoplakia Kaposi’s sarcoma
HIV infection to -> AIDS
Diseases are predictive of the progression to AIDS:
Oral Candidiasis Oral Hairy Leukoplakia
Kaposi’s sarcoma
Epidemiology Worldwide distribution
ESCALATING EPIDEMIC !!!
Source: WHO/UNAIDS/UN The Millennium Development Goals Report, 2009, p.32 and WHO.
Status in India
Blood Detection TestsHIV enzyme-linked immunosorbent assay (ELISA)
Screening test for HIVSensitivity > 99.9%
Western blot Confirmatory testSpeicificity > 99.9% (when combined with ELISA)
HIV rapid antibody test Screening test for HIVSimple to perform
Absolute CD4 lymphocyte count
Predictor of HIV progressionRisk of opportunistic infections and AIDS when <200
HIV viral load tests Best test for diagnosis of acute HIV infectionCorrelates with disease progression and response to HAART
Urine Testing
Urine Western Blot As sensitive as testing
blood Safe way to screen for HIV Can cause false positives in
certain people at high risk for HIV
Oral Testing
Orasure The only FDA approved
HIV antibody. As accurate as blood
testing Draws blood-derived
fluids from the gum tissue.
NOT A SALIVA TEST!
Treatment Options
HAART = Highly Active Anti-Retroviral Treatment
Antiretroviral Drugs (HAART)
Nucleoside Reverse Transcriptase inhibitorsAZT (Zidovudine), Lamivudine
Non-Nucleoside Transcriptase inhibitorsViramune (Nevirapine)
Protease inhibitorsNorvir (Ritonavir), Indinavir (Crixivan)
HEALTH CARE FOLLOW UP OF HIV INFECTED PATIENTSFor all HIV-infected individuals: CD4 counts every 3–6 months Viral load tests every 3–6 months and 1 month
following a change in therapy Toxoplasma IgG serology CMV IgG serology Pneumococcal vaccine Influenza vaccine in season Hepatitis B vaccine for those who are HBsAb-
negative Haemophilus influenzae type b vaccination Papanicolaou smears every 6 months for women
A Vaccine May Be the Only Way to Stop the HIV/AIDS Epidemic
Why AIDS does not fit the paradigm for classic vaccine development• Classic vaccines mimic natural immunity against reinfection generally seen
in individuals recovered from infection; there are no recovered AIDS patients.
• Most vaccines protect against disease, not against infection; HIV infection may remain latent for long periods before causing AIDS.
• Most vaccines protect for years against viruses that change very little over time; HIV-1 mutates at a rapid rate and efficiently selects mutant forms that evade immunity.
• Most effective vaccines are whole-killed or live-attenuated organisms; killed HIV-1 does not retain antigenicity and the use of a live retrovirus vaccine raises safety issues.
• Most vaccines protect against infections that are infrequently encountered; HIV may be encountered daily by individuals at high risk.
• Most vaccines protect against infections through mucosal surfaces of the respiratory or gastrointestinal tract; the great majority of HIV infection is through the genital tract.
• Most vaccines are tested for safety and efficacy in an animal model before trials with human volunteers; there is no suitable animal model for HIV/AIDS at present.
Vaccine strategies under study
Vaccine
constituentsStatus Advantages Disadvantages
Viral surface proteins, gp120
In phase I and II trials, which examine safety
Safe and simple to prepare
Vaccine –elicited antibodies have failed to recognize HIV from patients
Live vector viruses
In phase II trials Markers can control amount and kinds of viral proteins produced
Complicated to prepare
Combinations of elements, such as pure gp120 protein plus canarypox vector
In phase II trials Should stimulate both arms of the immune response at once
Complicated to prepare