عدد المساهمات : 907
تاريخ التسجيل : 01/08/2008
|موضوع: الشرح الكامل عن HIV الخميس 18 سبتمبر - 2:53|| |
Human Immunodeficiency Virus (HIV)
Human Immunodeficiency Virus (HIV) presents a complex knot
for scientists to unravel. After initial contact and attachment to a cell
of the immune system (e.g. lymphocytes, monocytes), there is a cascade of
intracellular events. The endproduct of these events is the production of
massive numbers of new viral particles, death of the infected cells, and
ultimate devastation of the immune system. However, the knot IS becoming
unraveled. These pages attempt to simplify HIV infection at the cellular
level. The following diagram shows a number of steps from initial attachment
of a viral particle to a lymphocyte through budding of new viruses from that
|1. ATTACHMENT |
2. REVERSE TRANSCRIPTION
From viral RNA to DNA
a. Viral DNA joins host DNA
b. Making multiple viral RNAs
Producing viral proteins
5. VIRAL PROTEASE
Cleaving viral proteins
ttachment to the Lymphocyte Membrane
On the surface membrane of all living cells are complex protein structures
A receptor is often compared to a lock into which a
specific key or "ligand" will fit. There are at least two receptors on
T-lymphocytes to which the human immunodeficiency virus (HIV) sticks.
The primary receptor, called "CD4", is shown on the right in the
diagram. But a second receptor that loops through the cell membrane 7
times is critical for infection to occur.
HIV infection of a lymphocyte requires attachment of the virus to the
cell membrane through both of these "ligand-receptor" links.
In cells whose "7-transmembrane receptor" is different, the HIV "key" no
longer matches the lymphocyte "lock"
and attachment is incomplete. Those cells may avoid infection by HIV.
Entry of the Viral RNA
Tight attachment of the viral particle to receptors on the lymphocyte membrane enables
fusion with the cell membrane. The viral contents, including viral
RNA (shown in yellow) then empty into the cell's cytoplasm.
Like other viruses that infect human cells, HIV commandeers the
host's machinery to make multiple copies of itself.
Reverse Transcription: Converting viral RNA into DNA
| ||Viral RNA (yellow) |
An enzyme (protein) that's part of the human immunodeficiency virus
reads the sequence of viral RNA nucleic acids that have entered the host
cell and transcribes the sequence into a complementary DNA sequence.
That enzyme is called "reverse
. Without reverse transcriptase, the viral genome couldn't become incorporated
into the host cell, and couldn't reproduce.
Reverse transcriptase sometimes makes mistakes reading the RNA sequence. The
result is that not all viruses produced in a single infected cell are alike.
Instead, they end up with a variety of subtle molecular differences in their
surface coat and enzymes. Vaccines, which induce the production of antibodies
that recognize and binding to very specific viral surface molecules, are an
unlikely player in fighting HIV, because throughout infection, HIV surface
molecules are continually changing.
AZT-like Drugs Inhibit Reverse Transcription
|Reverse Transcriptase Inhibitor (red) |
The first major class of drugs found useful in slowing HIV infections
are collectively called "reverse transcriptase inhibitors".
These include AZT, 3TC, d4T, ddc, and ddl that act by blocking the recoding
of viral RNA into DNA. The chameleon-like nature of HIV, however, limits
their continued effectiveness.
Integration of Viral DNA
Once the viral RNA has been reverse-transcribed into a strand of DNA,
the DNA can then be integrated (inserted) into the DNA of the lymphocyte.
The virus has its own enzyme called "integrase"
that facilitates incorporation of the viral DNA into the host cells DNA.
The integrated DNA is called a provirus.
Transcription: Back to RNA
As long as the lymphocyte is not activated or "turned-on",
nothing happens to the viral DNA. But if the lymphocyte is activated, transcription
of the viral DNA begins, resulting in the production of multiple copies
of viral RNA. This RNA codes for the production of the viral proteins and
enzymes (translation) and will also be packaged later as new viruses.
Translation: RNA >>> Proteins
There are only 9 genes in the HIV RNA. Those genes have the code necessary
to produce structural proteins such as the viral envelope and core plus enzymes
like reverse transcriptase, integrase, and a crucial enzyme called a protease.
When viral RNA is translated into a polypeptide sequence, that sequence is
assembled in a long chain that includes several individual proteins (reverse
transcriptase, protease, integrase). Before these enzymes become functional,
they must be cut from the longer polypeptide chain. Viral protease cuts
the long chain into its individual enzyme components which then facilitate
the production of new viruses.
Inhibitors of this viral protease can be used to fight
HIV infection. By blocking the ability of the protease to cleave the
viral polypeptide into functional enzymes, protease inhibitors interfere
with continued infection.
Mutations enable HIV to avoid treatments that involve only one drug,
so there is growing use of multiple-drug therapies in which both a protease
inhibitor AND a reverse transcript inhibitor are combined.
Assembly and Budding
Finally, viral RNA and associated proteins are packaged and released from
the lymphocyte surface, taking with them a swatch of lymphocyte membrane containing
viral surface proteins. These proteins will then bind to the receptors on other
immune cells facilitating continued infection.
Budding viruses are often exactly like the original particle that initially
infected the host. In the case of HIV, however, the resulting viruses exhibit
a range of variations which makes treatment difficult.