Tetraspanins regulate cell-to-cell transmission of HIV-1
ABSTRACT The presence of the tetraspanins CD9, CD63, CD81 and CD82 at HIV-1 budding sites, at the virological synapse (VS), and their enrichment in HIV-1 virions has been well-documented, but it remained unclear if these proteins play a role in the late phase of the viral replication cycle. Here we used overexpression and knockdown approaches to address this question.
Neither ablation of CD9, CD63 and/or CD81, nor overexpression of these tetraspanins was found to affect the efficiency of virus release. However, confirming recently reported data, tetraspanin overexpression in virus-producing cells resulted in the release of virions with substantially reduced infectivity. We also investigated the roles of these tetraspanins in cell-to-cell transmission of HIV-1. Overexpression of CD9 and CD63 led to reduced cell-to-cell transmission of this virus. Interestingly, in knockdown experiments we found that ablation of CD63, CD9 and/or CD81 had no effect on cell-free infectivity. However, knockdown of CD81, but not CD9 and CD63, enhanced productive particle transmission to target cells, suggesting additional roles for tetraspanins in the transmission process. Finally, tetraspanins were found to be downregulated in HIV-1-infected T lymphocytes, suggesting that HIV-1 modulates the levels of these proteins in order to maximize the efficiency of its transmission within the host.
Altogether, these results establish an active role of tetraspanins in HIV-1 producer cells.
Full-textDOI: · Available from: Marie Lambele, Jul 05, 2015
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ABSTRACT: Dendritic cells (DCs) play a key role in the initial infection and cell-to-cell transmission events that occur upon HIV-1 infection. DCs interact closely with CD4(+) T cells, the main target of HIV-1 replication. HIV-1 challenged DCs and target CD4(+) T cells form a virological synapse that allows highly efficient transmission of HIV-1 to the target CD4(+) T cells, in the absence of productive HIV-1 replication in the DCs. Immature and subsets of mature DCs show distinct patterns of HIV-1 replication and cell-to-cell transmission, depending upon the maturation stimulus that is used. The cellular and viral mechanisms that promote formation of the virological synapse have been the subject of intense study and the most recent progress is discussed here. Characterizing the cellular and viral factors that affect DC-mediated cell-to-cell transmission of HIV-1 to CD4(+) T cells is vitally important to understanding, and potentially blocking, the initial dissemination of HIV-1 in vivo.Advances in Experimental Medicine and Biology 01/2013; 762:109-30. DOI:10.1007/978-1-4614-4433-6_4 · 2.01 Impact Factor
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ABSTRACT: Tetraspanin proteins on host cells are involved in the pathogenesis of infectious diseases at different stages. In this review, we will focus on tetraspanins expressed in the immune system and the role they play in the defense to viral, bacterial, parasitic and fungal infections.Microbes and Infection 11/2009; 12(2):106-12. DOI:10.1016/j.micinf.2009.11.001 · 2.73 Impact Factor