45 - HIV - genetics, serology

There are three genes in HIV which are characteristic of all retroviruses:

* gag:
o encodes a precursor protein (Pr55)
o cleavage yields:
+ p17 matrix protein
+ p24 capsid protein
+ p9 nucleocapsid protein
+ p6

* pol encodes reverse transcriptase, endonuclease and protease activities

* env:
o encodes a precursor protein p160
o cleavage yields:
+ p41 a transmembrane protein which anchors p120
+ p120 binds non-covalently to p41 and acts as the CD4 receptor

In addition to these typical genes there are other regulatory genes.

The HIV genome codes for several regulatory proteins, including:

* tat:
o accelerates the rate of viral transcription

* rev:
o rev regulates the balance of transcription of the regulatory proteins (tat & rev) versus the structural proteins (gag, pol & env)

* nef:
o causes downregulation of the expression of CD4 on the host cell surface

* vpr, vpu & vif:
o the roles of these proteins are not well characterised

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HIV LAB TESTS

These include:

* HIV culture - in stimulated lymphocytes
* HIV antigen - p24 antigen test
* HIV nucleic acid - using the polymerase chain reaction
* HIV antibody - ELISA or Western blot

HIV antibody tests are used for diagnosis and screening.

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SEROLOGY

Approximate time from exposure (weeks) to the development of serological markers of HIV infection.

* p24 antigen 1-4 weeks
* IgM antibody 3-10 weeks
* IgG antibody 4-18 weeks

Following HIV exposure there is a variable pre-antibody stage followed by seroconversion.

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SUBTYPES

The causative agent of AIDS was originally identified as HTLV-3 in 1983. This is now termed HIV-1 and is the predominant serotype worldwide.

In 1985 a second serotype, known as HIV-2, was identified. It is more closely related to the Simian Immunodeficiency Virus (SIV) of macaques. HIV-2 has been found in East Africa, Asia, Southern Europe, Latin America and North America, but it is most extensive in Western African countries.

Compared with HIV-1, HIV-2 is characterised by lower rates of sexual and perinatal transmission, decreased CD4 cell killing, slower progression to AIDS and death, and relative geographical confinement.