Abstract
BackgroundThere is evidence suggesting that actin binding to HIV-1 encoded proteins, or even actin dynamics themselves, might play a key role in virus budding and/or release from the infected cell. A crucial step in the reorganisation of the actin cytoskeleton is the engagement of various different GTP binding proteins. We have thus studied the involvement of GTP-binding proteins in the final steps of the HIV-1 viral replication cycle.ResultsOur results demonstrate that virus production is abolished when cellular GTP binding proteins involved in actin polymerisation are inhibited with specific toxins.ConclusionWe propose a new HIV budding working model whereby Gag interactions with pre-existing endosomal cellular tracks as well as with a yet non identified element of the actin polymerisation pathway are required in order to allow HIV-1 to be released from the infected cell.
Highlights
There is evidence suggesting that actin binding to HIV-1 encoded proteins, or even actin dynamics themselves, might play a key role in virus budding and/or release from the infected cell
Expression of the HIV-1 Gag precursor, by HeLa-CD4 cells, resulted in viral-like particles (VLP) released to the media (Fig. 1A and Material and Methods)
The overall intracellular Gag production was not significantly modified in these experimental conditions, as shown by p24 quantification and western blot analysis of the soluble fraction of detergent lysed treated cells (Fig. 1B, C). These results show that Pr55gag release was abolished when small GTP binding proteins such as Cdc42, Rac, and/or Rho were inhibited
Summary
There is evidence suggesting that actin binding to HIV-1 encoded proteins, or even actin dynamics themselves, might play a key role in virus budding and/or release from the infected cell. We have studied the involvement of GTP-binding proteins in the final steps of the HIV-1 viral replication cycle. The final step in HIV-1 replication cycle is the release of nascent viral particles from the infected cell. In this way, HIV-1 acquires its lipid bilayer envelope by budding through the plasma membrane of infected T CD4+ cells. A discrete functional sequence, referred to as the L domain encoded by a PTAP motif in the C-terminal, p6 portion of the Gag precursor, catalyses the pinching off of virus particles from the plasma membrane. Further work has shown that the interaction between this viral domain and the cellular cytosolic Tsg101 (the tumor susceptibility gene) molecule, that functions in the biogenesis of the multivesicular body (MVB) endosomal compartment [5], is critical for nascent virus detachment from the plasma membrane of the infected T cell [reviewed in 6]
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