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20 July 2004

How HIV infection begins

The HI virus is very clever and very cunning, once inside your body, it "hijacks" the cells that manage your immune system and slowly builds up a reservoir of inactive viral cells that lie in wait.

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What does HIV do to the CD4 cells?
HIV is a devious enemy: It attacks the CD4 cells (or generals of the immune system) directly, which means that the immune system is leaderless and defenceless.

The antibodies that are formed during this process to try and fight off the enemy, are completely powerless against HIV because the HI viruses hide in CD4 cells relatively undetectable.

The HI viruses now use the mechanisms of the CD4 cell to manufacture copies of themselves, or to replicate. HIV literally hijacks the most important immune cells in our bodies - the CD4 cells - and use them as virus factories.

And in the end, the immune system collapses - and the body has no defence against invading organisms.

The “gates of the immune system” are thrown open and the body is attached by any “passerby” infection such as tuberculosis, malaria, certain types of cancer, bacteria causing diarrhoea - the list is endless.

In the end, people with Aids die of opportunistic infections or diseases. Opportunistic infections are caused by organisms which do not normally attack a healthy immune system, but that “takes the opportunity” to attack a depressed immune system.

How HIV “hijacks” a CD4 cell
The HI virus is very clever and very cunning, once inside your body, it "hijacks" the cells that manage your immune system and slowly builds up a reservoir of virus infected but inactive cells that lie in wait.

Step 1:
HIV comes with a “key” (glycoprotein projections on its outside shell) and these keys fit into only one specific type of “lock” (receptor sites), and CD4 cells have these specific CD4 receptors (or locks) on its surface. The virus binds or attaches itself firmly to the outer layer (or cell membrane) of the CD4 cell (onto a CD4 receptor on the host cell wall).

Step 2:
Interaction with co-receptors takes place, leading to anchorage of the virus. The CD4 cell and the HI virus now join membranes, fusion takes place, and the virus can now enter the cell.

Step 3:
The virus sheds its outer layer, and injects its RNA (genetic material) into the CD4 cell.

Step 4:
A process called reverse transcription takes place (remember HIV is a retrovirus, which means that its genetic material is RNA and not DNA - therefore in order to use the host cell’s machinery to make more viruses, it has to change its RNA to DNA first).

Step 5:
The viral DNA now joins with the cell’s DNA in the core of the cell, and it produces more viral RNA and viral proteins.

Step 6:
With the help of the enzyme, protease, the new viral proteins and viral RNA join together or assemble to form new viruses.

Step 7:
As the new HI viruses bud from the cell, they usually kill the hijacked cell in the process. They then move out into the bloodstream or surrounding tissue to infect more cells - and repeat the whole process over again

What does it mean that HI viruses build up a reservoir?
HI viruses hide in the Memory T cells where it builds up a latent reservoir. This means that the viruses “lie in waiting”, latent or dormant - until they get active at a later stage. This latent reservoir in Memory T cells is one of the reasons why HIV cannot completely be eradicated by drugs.

What is meant by HIV Subtype C?
There are many HIV subtypes, and HIV-1 subtype C is predominant in South Africa. Vaccine development in South Africa is therefore based on HIV-1 subtype C.

HIV-1 subtype C is a very virulent virus, and the following problems with HIV-1 subtype C, were identified at the Barcelona AIDS conference (2002):

  • it has a very high prevalence rate (20-40%)
  • it carries a higher risk of vertical transmission (from mother to baby) than other subtypes
  • there are higher viral loads in the blood with subtype C
  • subtype C has higher levels of viral diversity
  • extent to which subtype C mutates is very high
  • subtype C spreads faster than any of the other subtypes

Intersubtype recombinant viruses are contributing substantially to the global epidemic.

 
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