Human Immunodeficiency Virus (HIV) :



I INTRODUCTION
member of the Retroviridae family of viruses (commonly known as retroviruses), and classified in the subfamily lentiviruses. Human infection with HIV results in a complex clinical disease known as acquired immune deficiency syndrome (AIDS), which may take ten years or more to develop. Three groups of scientists are credited with discovering HIV in association with AIDS: first in 1983 was Luc Montagnier’s group at the Pasteur Institute in Paris, followed by Robert Gallo’s group at the National Cancer Institute, and then a group headed by Jay Levy at University College San Francisco. The viruses have several common features: a long asymptomatic period before the onset of clinical disease, infection of blood cells and the nervous system, and an association with suppression of the immune system. Although no preventative AIDS vaccine as yet exists, scientists from Britain, France, and the United States announced in February 1999 that the source of the HIV virus is a subspecies of endangered chimpanzee, Pan troglodytes troglodytes, that is native to west Central Africa. It is believed that the virus passed from the chimpanzees—who have developed an immunity to the virus—via human beings hunting them for food.


II STRUCTURE
Retroviruses are classified by their unique feature: the need to convert their genomic RNA into DNA (the process of reverse transcription) using an enzyme that they carry (reverse transcriptase). The outer surface of HIV is a lipid “envelope” derived from the cell membrane. Protruding from the surface are the viral transmembrane glycoprotein (gp41) and the envelope glycoprotein (gp120) that allow HIV to bind and fuse with a target cell. Within the envelope, the viral core protein, p17, forms the matrix of the virion particle and the core protein, p24, forms an inner cylindrically shaped nucleoid. The nucleoid contains two strands of viral genomic RNA (the genetic material of HIV) and the associated reverse transcriptase enzyme.


III HOW HIV CAUSES INFECTION
HIV infects a human cell by binding its envelope glycoprotein gp120 to molecules on the surface of the cell. Only cells that carry the appropriate molecules are susceptible to infection by HIV. In the 1980s scientists quickly recognized that a molecule called CD4, which is found particularly on certain T-lymphocytes (a type of white blood cell), was the primary binding site, but it was only in 1996 that the other co-receptors were also identified. Fusion of the virus with the cell membrane permits the viral nucleoid to enter the cell.
One of the co-receptors is called chemokine receptor 5 (CKR5). Because of their inherited genetic make-up, about 14 per cent of Caucasians have unusually small numbers of these receptors on the surface of their cells and a smaller proportion do not express CKR5 on their cells at all, rendering these cells less susceptible to infection with HIV. Studies suggest that this may help to explain why some people appear to be resistant to HIV infection and remain HIV-negative despite multiple exposures to the virus, and why some HIV-positive people experience slower disease progression than others.
As HIV disease progresses, HIV variants called syncytium-inducing (SI) strains evolve within the individual’s body. SI variants can use an additional co-receptor on human cells, called fusin. This may allow HIV to infect a wider range of cells and may help to explain why the emergence of SI variants is associated with a worse prognosis. Again, a small proportion of Caucasians (about 1 per cent) do not produce this co-receptor.
Once fusion has taken place, reverse transcription then occurs to convert the viral genomic RNA into double-stranded DNA. The viral DNA is transported to the cell nucleus and is integrated, or inserted, into the normal cellular chromosomal DNA. When the right activation signals are present, the process of making new virions begins. Using the replication machinery of the host cell, the integrated viral DNA is transcribed to make messenger RNA (mRNA) and new strands of viral genomic RNA. The viral mRNA is then translated into new viral proteins and assembly of new virions takes place within the cell. The new HIV particles are released by budding from the cell surface, taking a piece of the cell membrane as their envelope.
HIV replication can directly kill CD4 T-lymphocytes. The loss of these cells paralyses the immune system and is one mechanism by which HIV infection causes AIDS. Recent advances in the management of HIV infection have led to the use of a new class of anti-retroviral drugs known as protease inhibitors. These drugs are enabling HIV-positive patients to live longer and experience an improved quality of life. As the protease enzyme is responsible for the maturation of newly formed HIV virion particles, inhibiting this enzyme has the effect of reducing the infectivity of the resultant virions.