Human immunodeficiency virus type 1 envelope proteins traffic toward virion assembly sites via a TBC1D20/Rab1-regulated pathway

Dikla Nachmias,Marcelo Ehrlich,Eran Bacharach,Ella H Sklan

doi:10.1186/1742-4690-9-7

Dikla Nachmias, Marcelo Ehrlich + Show 2 more

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https://doi.org/10.1186/1742-4690-9-7

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Journal: Retrovirology	Publication Date: Jan 19, 2012
Citations: 18	License type: cc-by

Affiliation: Tel Aviv University

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BackgroundThe cellular activity of many factors and pathways is required to execute the complex replication cycle of the human immunodeficiency virus type 1 (HIV-1). To reveal these cellular components, several extensive RNAi screens have been performed, listing numerous 'HIV-dependency factors'. However, only a small overlap between these lists exists, calling for further evaluation of the relevance of specific factors to HIV-1 replication and for the identification of additional cellular candidates. TBC1D20, the GTPase-activating protein (GAP) of Rab1, regulates endoplasmic reticulum (ER) to Golgi trafficking, was not identified in any of these screens, and its involvement in HIV-1 replication cycle is tested here.FindingsExcessive TBC1D20 activity perturbs the early trafficking of HIV-1 envelope protein through the secretory pathway. Overexpression of TBC1D20 hampered envelope processing and reduced its association with detergent-resistant membranes, entailing a reduction in infectivity of HIV-1 virion like particles (VLPs).ConclusionsThese findings add TBC1D20 to the network of host factors regulating HIV replication cycle.

Highlights

The cellular activity of many factors and pathways is required to execute the complex replication cycle of the human immunodeficiency virus type 1 (HIV-1)
Rab1, which cycles between active GTP-bound and inactive GDP-bound forms [10], and is present as Rab1a/b isoforms, regulates the early secretory pathway
To investigate if Env maturation and trafficking are regulated by TBC1D20 and occur via Rab1-dependent pathway, we exploited the effect induced by imbalanced expression of TBC1D20 on Rab1-mediated transport, and probed for the infectivity of HIV-1 virion like particles (VLPs) in such conditions

Summary

Introduction

The cellular activity of many factors and pathways is required to execute the complex replication cycle of the human immunodeficiency virus type 1 (HIV-1). To investigate if Env maturation and trafficking are regulated by TBC1D20 and occur via Rab1-dependent pathway, we exploited the effect induced by imbalanced expression of TBC1D20 on Rab1-mediated transport, and probed for the infectivity of HIV-1 VLPs in such conditions. TBC1D20 overexpression decreased the infectivity of VLPs suggesting that VSV-G and HIV Env traffic through a Rab1-sensitive pathway.

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