The cellular and molecular basis of the Nef requirement for HIV-1 infectivity

Rosa, Annachiara (2016) The cellular and molecular basis of the Nef requirement for HIV-1 infectivity. PhD thesis, University of Trento.

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Abstract

Nef is an HIV -1 accessory protein with a fundamental role for virus replication in vivo and for the development of AIDS. Among its several activities, Nef is essential for full HIV-1 infectivity, a function highly prominent in lymphoid cells. So far, the mechanism by which Nef promotes HIV-1 infectivity has remained elusive. Over the course of 3 years, my PhD research activity has led to the identification of the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as potent inhibitors of HIV-1 infectivity counteracted by the viral protein Nef [Rosa et al., 2015]. SERINC5 is predominantly localized on the plasma membrane where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef relocalizes SERINC5 to an endosomal compartment preventing its incorporation into HIV-1 particles. The ability to counteract SERINC5 is conserved in Nef proteins encoded by different primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus (MLV). These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 in the interaction of the host with retroviral pathogens. Remarkably, SERINC5 potently inhibits HIV-1 even in the presence of Nef in a dose-dependent manner, suggesting that this cellular factor might be exploited as an anti-HIV-1 therapeutic gene.

Item Type:Doctoral Thesis (PhD)
Doctoral School:Biomolecular Sciences
PhD Cycle:28
Subjects:Area 05 - Scienze biologiche > BIO/11 BIOLOGIA MOLECOLARE
Repository Staff approval on:03 Mar 2016 10:19

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