Ljubljana/HIVbacground
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Eventually, clinically apparent diseases develop, such as neoplasms or opportunistic infections. These are a consequence of rapid viral proliferation in CD4 infected cells and their subsequent destruction which weakens the immune system. The onset of these symptoms is known as the progression to AIDS.<br><br> | Eventually, clinically apparent diseases develop, such as neoplasms or opportunistic infections. These are a consequence of rapid viral proliferation in CD4 infected cells and their subsequent destruction which weakens the immune system. The onset of these symptoms is known as the progression to AIDS.<br><br> | ||
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| + | Despite enormous efforts to find the ultimate cure for AIDS there is no efficient treatment that could totally eliminate HIV. The main reason for not being able to develop a useful drug is the lack of proofreading replication enzymes in HIV. Consequently, mutations occur changing the properties of HIV molecules. Thus, resistance evolves quickly, making many existing drugs useless. Nevertheless, certain therapeutics and drug cocktails can slow down AIDS progression and provide better life for those infected with HIV. Another problem in AIDS treatment is the price of therapeutics; only a fraction of infected population can afford the expensive treatment.<br><br> | ||
Revision as of 20:27, 24 October 2007
HIV-1 Infection Background
HIV primarily infects cells that are important in human immune response: T-cells, macrophages and dendritic cells. By replicating itself in T-cells it destroys them and thus weakens the immune system.
Approximately one to three months after infection a specific immune response develops, causing the number of viral particles to decrease and the CD4 cell count rebounces. However, the immune response is unable to clear the infection completely, and HIV-infected cells persist in the lymph nodes as viral DNA integrated in the host genome. This period of clinical latency may last for as long as 10 years, but there is still a a high level of ongoing viral replication.
Eventually, clinically apparent diseases develop, such as neoplasms or opportunistic infections. These are a consequence of rapid viral proliferation in CD4 infected cells and their subsequent destruction which weakens the immune system. The onset of these symptoms is known as the progression to AIDS.
Despite enormous efforts to find the ultimate cure for AIDS there is no efficient treatment that could totally eliminate HIV. The main reason for not being able to develop a useful drug is the lack of proofreading replication enzymes in HIV. Consequently, mutations occur changing the properties of HIV molecules. Thus, resistance evolves quickly, making many existing drugs useless. Nevertheless, certain therapeutics and drug cocktails can slow down AIDS progression and provide better life for those infected with HIV. Another problem in AIDS treatment is the price of therapeutics; only a fraction of infected population can afford the expensive treatment.
Virus Life Cycle
HIV (human immunodeficiency virus) is a retrovirus, Its genome is composed of two single stranded RNA molecules. It has a gag/pol/env organization; gag genes (group specific antigen) code for structural proteins, env for proteins that build viral envelope, while pol genes are responsible for viral reproduction (they contain genes for reverse transcriptase, integrase and HIV protease).
HIV envelope consists of lipids and viral glycoproteins gp120 and gp41, which are crucial for binding of HIV to the host cell membrane and for entering into the cell. Inserted into the lipid bilayer are also other glycoproteins that guarantee firmness and protective function of the viral envelope. Gp120 binds to receptors (CD4) on the host cell surface, but additional co-receptors like chemokine receptors (CCR5, CXCR4) are also required for successful entry of HIV. Mutations in co-receptor genes can cause immunity – if HIV cannot enter host cells, HIV infection is prevented, and AIDS cannot develop.
The characteristic retroviral enzyme is reverse transcriptase, which transcripts viral RNA into DNA. Only DNA can integrate into host cell genome – this is the crucial step in expressing viral proteins that are needed for assembly of new viral particles. Viral gag and gag/pol genes are expressed as polyprotein; until this polyprotein is cut into functional units, it exerts no biological function. Polyprotein clipping is done by HIV protease. The resulting polyprotein fragments represent functional enzymes and structural proteins.
Transcription of viral RNA into DNA and processing of the viral polyprotein are two most important steps in HIV replication cycle. These are thus obvious targets for HIV therapeutics. Inhibitors of reverse transcriptase and HIV protease are currently used to treat acute HIV infection.
