Retroviridae. HIV 1 And HIV 2

Question 1

Classification

Answer 1

Family: Retroviridae

Genus —> Lentivirus

Species —> HIV 1
Species —> HIV 2

Two species of HIV infect humans
HIV 1 —> more virulent, easily transmitted, causes the majority of infections worldwide
HIV 2 —> less virulent, confined to West Africa

Question 2

Characteristics

Answer 2

• Enveloped virus
• Diploid +ssRNA
• RNA dependent DNA polymerase (reverse transcriptase) makes a DNA copy of the genome, which integrates into host cell DNA
• precursor polypeptides must be cleaved by virus-encoded protease to produce functional viral proteins

Antigenicity of gp 120 protein changes rapidly —> many serotypes

Question 3

Transmission

Answer 3

Transfer by body fluids (e.g. blood and semen)

• sexual contact
• sharing of needles
• blood transfusion
• organ transplantation

Between mother and child:
- trans-placental transmission 
- perinatal transmission 
> childbirth
> breast feeding

Question 4

Risk factor groups

Answer 4

• homosexual or bisexual men
• intravenous drug users
• heterosexual individual
• recipients of blood or organ transplants
• hemophiliacs
• children

Question 5

Pathogenesis

Answer 5

• 1st —> infection of macrophages = PRODOME PHASE
• 2nd —> infection of CD4 cells —> leads to a drop in CD4 cells —> LATENT PHASE

Two receptors are required for HIV to enter cells:
> (1) CD4 receptors found primarily on helper T cells:
- HIV infects and kills helper T cells, which predisposes to opportunistic infections
- other cells bearing CD4 receptor on the surface (e.g. astrocytes) are infected also
> (2) second receptor for HIV is a chemokine receptor such as CCR5 (early stages) or CXCR4 (late stages)

• The NEF protein is an important virulence factor.
  It reduces MHC I protein synthesis, thereby reducing the ability of cytotoxic T cells to kill HIV infected cells
  [Cytotoxic T cells are the main host defense against HIV]

Question 6

Disease

Answer 6

1) primary infection = prodrome (flu-like symptoms)

2) clinical latency
- decrease in CD4 cell count

3) AIDS
- CD4 count drops <200
Early stages: Kaposi’s sarcoma
Advanced stage: CD4 < 50 —> risk of death

Question 7

Microbiological diagnosis

Answer 7

• HIV can be isolated from blood or semen, but this procedure is not routinely available

Diagnosis is usually made by:

• ELISA to detect antibodies
• Western blot as confirmatory test —> gp24, gp41 and gp120 are simultaneously detected —> positive!
• PCR viral load assay to determine the amount of HIV RNA in the plasma
• a high viral load predicts a more rapid progression to AIDS than a low viral load

PCR based assays can also detect viral RNA in infected cells, which is useful to detect early infections before antibody is detectable

Question 8

Treatment

Answer 8

Highly active antiretroviral therapy (HAART) consists of a combination of three drugs:
- either two nucleotide [NRTI] reverse transcriptase inhibitors (lamivudine and zidovudine) and one protease inhibitor (fosamprenivir)

• or, the same two NRTI (lamivudine and Zidovudine) and one [NNRTI] non-nucleotide reverse transcriptase inhibitor (efsvirenz)

Maraviroc- inhibits CCR5 receptor

Treatment of the opportunistic infection depends on the organism

Question 9

Prevention

Answer 9

• screening of blood prior to transfusion for the presence of antibody
• “safe sex” including the use of condoms
• no vaccine

> Zidovudine is the best drug known to give during pregnancy —> reduction in 2/3 rd infection to neonates