Encapsidation of Staufen-2 Enhances Infectivity of HIV-1.

Kannan Balakrishnan,Sharmistha Banerjee,Tom Luedde,Carsten Münk,Krishnaveni Mohareer,Ananda Jaguva Vasudevan

doi:10.3390/v13122459

Kannan Balakrishnan, Sharmistha Banerjee + Show 4 more

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https://doi.org/10.3390/v13122459

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Abstract

Staufen, the RNA-binding family of proteins, affects various steps in the Human Immuno-Deficiency Virus (HIV-1) replication cycle. While our previous study established Staufen-2–HIV-1 Rev interaction and its role in augmenting nucleocytoplasmic export of RRE-containing viral RNA, viral incorporation of Staufen-2 and its effect on viral propagation were unknown. Here, we report that Staufen-2 interacts with HIV-1 Gag and is incorporated into virions and that encapsidated Staufen-2 boosted viral infectivity. Further, Staufen-2 gets co-packaged into virions, possibly by interacting with host factors Staufen-1 or antiviral protein APOBEC3G, which resulted in different outcomes on the infectivity of Staufen-2-encapsidated virions. These observations suggest that encapsidated host factors influence viral population dynamics and infectivity. With the explicit identification of the incorporation of Staufen proteins into HIV-1 and other retroviruses, such as Simian Immunodeficiency Virus (SIV), we propose that packaging of RNA binding proteins, such as Staufen, in budding virions of retroviruses is probably a general phenomenon that can drive or impact the viral population dynamics, infectivity, and evolution.

Highlights

HIV-1 relies on host cellular machinery for its infectivity and propagation
Staufen-2 Is Encapsidated into HIV-1 Virions, Enhancing Their Infectivity
To investigate if Staufen-2 is packaged into HIV-1 virions and modulates viral infectivity, we generated HEK293T cells that stably expressed Staufen-2 with a FLAG tag (Figure 1A)

Summary

Introduction

HIV-1 relies on host cellular machinery for its infectivity and propagation. HIV1 RNA associates with many host RNA binding proteins (RBPs) during its transport and translation. The molecular composition of HIV-1 RNA-associated RBP containing ribonucleoprotein (RNP) complexes undergo dynamic changes during virus propagation, associating with distinct host proteins at different stages, such as splicing, nuclear export of viral RNA, translation, assembly, and budding [1,2,3]. The cumulative impact of these interactions determines HIV-1 production and viral population dynamics. HIV-1 Gag plays a crucial role in viral RNA encapsidation and particle assembly. During this process, HIV-1 Gag associates with several host RBPs forming RNP complexes

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