Structure & Property

Transmission

Pathogenesis

Clinical findings

Laboratory diagnosis

Treatment

Family: retrovirus

Genome: single strand, 2 segments, +ve polarity RNA.

Genes:

- gag: core proteins – p24.

- pol: reverse transcriptase & integrase.

- env: envelop glycoproteins gp160 cleaved to gp 41 & gp120

- tat: enhances viral mRNA synthesis, suppress MHC class I expression.

Size: 100nm

Icosahedral nucleocapsid.

Enveloped virion with central wedge-shape core.

Two types:

- HIV-1

- HIV-2

HIV-1: main cause of the world-wide AIDS pandemic.

HIV-2: West Africa

Routes:

- sexual

- paraenterally by infected blood or blood products, needle-sharing among drug abusers.

- in utero from mother to child, perinatally or via breast milk.

Infected mothers transmit HIV to their babies in about 20% of cases:

- transplacentally: to cause infection in utero.

- during delivery or in the perinatal period.

- through breastfeeding.

Replication:

- binding of gp120 to CD4 protein on cell surface

- gp41 mediates fusion of viral envelope with cell membrane.

- virion RNA-dependent DNA polymerase transcribe genome RNA into dsDNA which integrates into host cell DNA.

- viral mRNA transcribed and cleaved.

- assembled virions released from cells by budding.

Pathology:

- infects helper T cells and kills them, resulting in suppression of cell-mediated immunity.

- virus causes disseminated infection and affect many organs.

- cells recruited into syncytia die.

- HIV-infected cells killed by immunologic attack by cytotoxic CD8 cells.

- HIV acts as a superantigen, activates many helper T cells.

Chronic infection for life.

Three stages of HIV infection:

Acute primary infection:

- often symptomless

- sometimes with an infectious mononucleosis-like illness some 2 weeks to 3 months after exposure with:

- fever, rash, sore throat, night sweats, malaise, lymphadenopathy, diarrhea and lymphocytosis.

Variable symptomless period:

- usually around 1-10 years.

- active viral replication in lymphoid tissues; mainly lymphocytes and macrophages.

- patients may show depressed counts of CD4 lymphocytes.

Symptomatic stage:

- leading into full-blown AIDS.

- presents with persistent lymphadenopathy and other infections associated with defective cell-mediated immunity:

- fever, diarrhea, fatigue, candidiasis, zoster, hairy leukoplakia of tongue

- idiopathic thrombocytopenic purpura.

Progression to AIDS correlates with:

- decrease in CD4 count

- appearance of p24 in blood.

AIDS:

- characterized by an extreme degree of immunodeficiency, with low and decreasing CD4 counts.

- results in a serious of opportunistic infections and certain tumors.

Symptoms of infected infants:

- failure to thrive

- fever, diarrhea, frequent infections.

- lymphadenopathy, lymphoid intestinal pneumonia

- parotitis

- hepatosplenomegaly

- progressive encephalopathy and dementia.

Tissue culture:

- grows in lymphocytes with variable CPE.

- cocultivation with certain other cells results in syncytium formation and allows easier detection of virus growth.

Diagnosis:

- detection by ELISA but there are some false-positives.

- definitive test is made by Western blot.

- positive test requires presence of bands at gp24, gp31, gp41, gp120.

PCR for the detection of:

- virus RNA in blood and other body fluids.

- virus load: quantification of amount of virus in blood to monitor progress of disease.

Infection in infants:

- difficult to diagnose because of persistent of maternal antibody in all babies born to infected mothers.

- HIV antibody persisting around 15 months is strong evidence of infection.

- use of PCR for detection or isolation of virus from the infant’s leukocytes.

Treatment aimed at two targets:

- HIV: AZT does not eradicate virus but improves survival.

- associated opportunistic infections and tumors are treated with antimicrobial drugs and chemotherapy.

Current treatment of choice: 2 nucleoside inhibitors and a protease inhibitor.

No vaccine is available.

Prevention:

- avoid exposure to virus: use of condoms, not sharing needles, discarding donated blood contaminated with HIV.

- AZT given perinatally to HIV-infected mothers who should not breast-feed.