The HIV Life Cycle
The HIV life-cycle is the story of how a single HIV virus particle infiltrates a cell and uses it to produce new HIV particles.
This isn't the whole story about HIV, of course. In order for a person to become infected with HIV, one or more virus particles must enter the body. These particles will be borne in fluid such as blood or semen, since the HIV virus cannot survive on its own outside the body.
Once inside the body they need to find their way to susceptible cells, where the HIV life-cycle proper begins.
Which sort of cells does HIV go for? Any cell carrying the CD4 protein on its surface (which we call a CD4+ cell) is susceptible, since CD4 is the main receptor for HIV. Different strains of HIV target different cells - but T cells and macrophages, both of which are CD4+, are two important targets for HIV.
Infiltrating a cell
The first step of the HIV life cycle is binding to the cell membrane, followed by membrane fusion, to get the virus particle's contents into the host cell.
Then follows reverse transcription of the HIV's genome from RNA into DNA, and its integration into the host genome.
HIV Genome
The full HIV genome is encoded on one long strand of RNA. (In a free virus particle, there are actually two separate strands of RNA, but they're exactly the same!)
This is the form it has when it is a free virus particle. When the virus is integrated into the host's DNA genome (as a provirus) then its information too is encoded in DNA.
The following image shows roughly how the genes are laid out in HIV (remember that HIV-1 and HIV-2 are quite different). Click on a gene's name for more information.
The genes in HIV's genome are as follows:
* gag (coding for the viral capsid proteins)
* pol (notably, coding for reverse transcriptase)
* (NB. gag and pol together can be expressed in one
long strand called "gag-pol")
* env (coding for HIV's envelope-associated proteins)
* And the regulatory genes: tat
* rev
* nef
* vif
* vpr
* vpu (N.B. not present in HIV-2)
* vpx (N.B. not present in HIV-1)
The HIV genome also has a "Long Terminal Repeat" (LTR) at each end of its genome - not quite a gene, but a sequence of RNA/DNA which is the same at either end and which serves some structural and regulatory purposes.
The human immune system
The mammalian immune system is a fantastic, and fantastically-complex, system. There are a number of cells specialised for particular jobs in recognising and defending against foreign materials that might enter the body (e.g. bacteria or viruses). Some of these cells also play roles in other procedures such as wound-healing. There are differences in the immune systems of different species - humans, primates, etc. - and since we're interested in HIV, we'll just look at the human immune system for now.
The following image shows a summary of the important cells and molecules in the human immune system - the top half of the picture represents detection of invaders, and the bottom half represents the defence which is triggered by that detection.
From our perspective of HIV, the most important cells are perhaps the lymphocytes - indeed, one specific type, called "T lymphocytes" or "T cells". They are the cells which HIV targets and infects. In ordinary immune function, T cells often work together with the other major type of lymphocyte: B lymphocytes or B cells. Notice the position of the helper T cells in the diagram (labelled TH) - they're in the middle, the key in the transition from detecting an invader to launching a defence against it.
Also important are macrophages, cells which effectively "eat" invaders. HIV does target macrophages, but to a much lesser extent than T cells.
Antibodies (immunoglobulins) aren't cells, but are molecules secreted by the immune system - molecules designed to latch on to invaders and to neutralise them in various ways, and also to trigger certain activities of the immune cells. You can see some of them indicated in the diagram, including various interleukins (labelled IL). Cytokines too are important molecules in the immune system - they are molecular signals emitted by lymphocytes and other cells.
Ways to stop it
How can we stop AIDS? This is such an important question, and there are so many possible answers.
Perhaps one of the best things to do would be to prevent HIV passing from one person to another?
Or, since we know know quite a lot about the life cycle of HIV, surely we can throw a spanner into the works? The HIV life cycle is a complex ballet of dozens of different types of molecules, so if we can trip up one single part of the dance, perhaps it won't be able to go on. This is the approach taken by many lines of research. Unfortunately it's not so simple to trip up HIV replication - mainly because it takes place in the human body, and any chemical which affects HIV replication runs the risk of causing unacceptable dangers and side-effects to the infected individual. Anti-HIV drugs are often developed to retard HIV's life cycle.
Perhaps we can help out our immune system somehow? It's the immune system which is supposed to deal with infections, after all, so perhaps we can beef it up, or train it specifically against HIV?
Or, in a turning of the tables, perhaps we could forget about trying to stop HIV infection, and try some treatment which means we can live with HIV infection without progressing on to AIDS? There are people who can catch HIV without getting AIDS - these are called "long-term nonprogressors" - so finding out how and why they don't get AIDS holds the possibility of our arranging it so everyone becomes a long-term nonprogressor....
Yet another possibility comes from the existence of individuals with the delta32 mutation, who seem to be immune to the most common forms of HIV-1. Could we induce a protective mutation in people's cells?
23 November 2009
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