Cornering HIV: Taking advantage of interactions between selective pressures

Summary Adaptive immune responses, cellular restrictive factors and antiretroviral drugs, target multiple regions in the Human Immunodeficiency Virus (HIV) proteome, imposing diverse pressures to viral adaptation. However, the virus is remarkably able to escape from these pressures as mutations are...

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Bibliographic Details
Published in:Medical hypotheses 2007, Vol.69 (2), p.422-431
Main Authors: Ávila-Ríos, S, Reyes-Terán, G, Espinosa, E
Format: Article
Language:English
Subjects:
Adaptation, Physiological - drug effects
Adaptation, Physiological - genetics
Adaptation, Physiological - immunology
Anti-HIV Agents - pharmacology
HIV - drug effects
HIV - genetics
HIV - growth & development
HIV - immunology
HIV Infections - drug therapy
HIV Infections - immunology
HIV Infections - metabolism
HIV Infections - virology
Humans
Internal Medicine
Virus Replication - genetics
Virus Replication - immunology
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Summary:Summary Adaptive immune responses, cellular restrictive factors and antiretroviral drugs, target multiple regions in the Human Immunodeficiency Virus (HIV) proteome, imposing diverse pressures to viral adaptation. However, the virus is remarkably able to escape from these pressures as mutations are selected. In many cases these mutants have diminished viral fitness. We propose that the concerted action of strategically placed agents and pressures in a host can limit HIV variation capacity while inhibiting its replication. These mechanisms would corner HIV by selecting conflicting adaptive mutations, each having a disadvantage in face of another selective pressure. This would keep the virus unable to efficiently escape the suppressive effects of selective pressures. Cornering between antiretroviral drugs and cytotoxic T lymphocytes may explain recent observations, and can be predicted and used in viral control strategies. This idea can be extended to numerous other identified sites in the viral genome that confer selective pressures. We describe these other sites and how they could be induced to interact in prophylactic or therapeutic cornering strategies, as well as their experimental verifications. Cornering would control HIV infection better than current strategies, focused on few, albeit important, sites in the HIV genome.
ISSN:0306-9877
1532-2777
DOI:10.1016/j.mehy.2006.12.012