Apobec3G strikes back - Researchers at the University of Geneva reveal a new defense mechanism against HIV
A research team led by Prof. Didier Trono, from the Department of Genetics and Microbiology at the University of Geneva, has discovered a mechanism that limits susceptibility to infection by retroviruses, the group of pathogens that comprises HIV. This defense mechanism stems from the action of Apobec3G, a protein present in human cells. The Geneva team shows that Apobec3G introduces fatal errors in the genetic information of retroviruses as they replicate, thus irreversibly blocking their spread. This constitutes an extremely efficient protection against most retroviruses. However, HIV fends off the attack through one of its own proteins, Vif, which neutralizes the antiviral effect of Apobec3G. These results, published this week in the online version of the scientific review Nature, open new avenues for the development of AIDS therapies targeting Vif function. Furthermore, they suggest that Apobec3G and perhaps other cellular proteins with related activities might play an important protective role against a broad range of viruses. A hallmark of the replication of retroviruses is the irreversible integration of their DNA into the chromosomes of the infected cell. This allows the hijacking of the cell machinery for the production of new viruses and, when the infected cell divides, for the transfer of the viral genetic information to its daughter cells. This largely explains why, once established, retroviral infections persist for life. HIV, the causative agent of AIDS, is the best known of all retroviruses. The team headed by Didier Trono, from the Department of Genetics and Microbiology at the University of Geneva, reveals this week that our body is endowed with an as yet unsuspected line of defense against retroviruses. This natural protection is mediated by a protein called Apobec3G, which is produced in particular in T lymphocytes and macrophages, the two subtypes of white blood cells that are the main targets of HIV in the body. Apobec3G introduces fatal errors in the genetic information of retroviruses as they replicate. These retroviruses are thereby irremediably damaged, and cannot express their infectious potential upon entering new cells. At the heart of the Geneva team's discovery is their finding that retroviruses produced in the presence of Apobec3G lose all replication potential due to the accumulation of mutations in their genome. However, whereas Apobec3G efficiently acts on a broad range of retroviruses, it is largely ineffective against HIV. The AIDS virus indeed carries a protein, Vif, which fends off the attack by neutralizing Apobec3G action. These results, published this week in the online version of Nature, represent a remarkable scientific advance in the fight against retroviruses in general and HIV in particular. New avenues are indeed opened for the development of AIDS therapies aimed at blocking Vif, thus the ability of HIV to overcome the antiviral effect of Apobec3G. Furthermore, this work suggests that Apobec3G and related cellular proteins might constitute an essential mechanism of protection against a broad range of viruses. For more information, do not hesitate to contact
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