The Human Immunodeficiency Virus (HIV)

The human immunodeficiency virus (HIV)

The HIV virus is roughly spherical and about one ten-thousandth of a millimetre across. Its outer envelope or coat is composed of a double layer of lipid envelope that bears numerous spikes (see Figure 2.1).

Each spike is composed of four molecules of ‘gp120’ and the same number of ‘gp41’ embedded in the membrane. Beneath the envelope is a layer ofmatrix protein that surrounds the core (capsid).The capsid has a hollow, truncated cone shape and is composed of another protein ‘p24’ within which lies the genetic material of the HIV virus –two strands of RNA consisting of about 9 749 nucleotide bases, integrase,

a protease, ribonuclease and two other proteins, ‘p6’ and ‘p7’ fit inside the viral core (Fauci, 1988; Greene, 1993; Stine, 2000).

HIV reverses the usual direction of genetic information within the host cell to produce protein.The process of protein synthesis in regular gene expression results from theDNA being copied intoRNA and the RNA is translated into specific proteins. With retroviruses like HIV, the RNA is copied using its reverse transcriptase (RT) enzyme. In the cytoplasm RT migrates along the RNA to produce a complementary strand of DNA. After completion of the first DNA strand the RT

begins constructing a second strand, using the first one as a template (Dimmock and Primrose, 1987; Fauci, 1988; Greene, 1993; Stine, 2000).

The double-stranded retroviral HIV DNA moves into the nucleus where it inserts into the host DNA and becomes a ‘provirus’. Infection of the cell is then permanent. The provirus can remain dormant for a long time. Its genes cannot be expressed until RNA copies are made by the host cell’s transcription machinery. Transcription starts when genetic switches at the ends of the provirus’ long terminal repeats

activate the cell’s RNA polymerase II. Regulatory proteins known as NF-kB/Rel (which are found in almost all human cells) bind with the long terminal repeats at the ends of the proviral RNA to activate the cell’s RNA polymerase and thereby cause transcription of the provirus to RNA (Greene, 1993). Some long terminal repeats possess regulatory genes (genes that control structural genes which produce

proteins) that contain a sequence for NF-kB and Sp1 binding sites that are shared by cellular regulator genes. Sequences recognised by NF-kB promote replication of HIV, cytomegalovirus, human Igk chain, and major histocompatibility antigen complex (MHC) classes

I and II, interleukin 1 (IL-1), and IL-2 (Chang, 1991). NF-kB/Rel regulatory proteins increase in production when the cell is exposed to foreign proteins or through hormones that control the immune system (Dimmock and Primrose, 1987; Fauci, 1988; Greene,1993; Stine, 2000). In essence, HIV uses our own biological machinery, NF-kB/Rel, to replicate itself and this co-option of human physiology  is initiated by foreign substances such as HIV infection.