TY - JOUR

T1 - Interactions between HIV-1 Gag and viral RNA genome enhance virion assembly

AU - Dilley, Kari A.

AU - Nikolaitchik, Olga A.

AU - Galli, Andrea

AU - Burdick, Ryan C.

AU - Levine, Louis

AU - Li, Kelvin

AU - Rein, Alan

AU - Pathak, Vinay K.

AU - Hu, Wei Shau

N1 - Publisher Copyright: © 2017 American Society for Microbiology.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious viruslike particles, and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA-Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.

AB - Most HIV-1 virions contain two copies of full-length viral RNA, indicating that genome packaging is efficient and tightly regulated. However, the structural protein Gag is the only component required for the assembly of noninfectious viruslike particles, and the viral RNA is dispensable in this process. The mechanism that allows HIV-1 to achieve such high efficiency of genome packaging when a packageable viral RNA is not required for virus assembly is currently unknown. In this report, we examined the role of HIV-1 RNA in virus assembly and found that packageable HIV-1 RNA enhances particle production when Gag is expressed at levels similar to those in cells containing one provirus. However, such enhancement is diminished when Gag is overexpressed, suggesting that the effects of viral RNA can be replaced by increased Gag concentration in cells. We also showed that the specific interactions between Gag and viral RNA are required for the enhancement of particle production. Taken together, these studies are consistent with our previous hypothesis that specific dimeric viral RNA-Gag interactions are the nucleation event of infectious virion assembly, ensuring that one RNA dimer is packaged into each nascent virion. These studies shed light on the mechanism by which HIV-1 achieves efficient genome packaging during virus assembly.

KW - Genome packaging

KW - HIV-1

KW - RNA genome

KW - Virus assembly

UR - http://www.scopus.com/inward/record.url?scp=85026328907&partnerID=8YFLogxK

U2 - 10.1128/JVI.02319-16

DO - 10.1128/JVI.02319-16

M3 - Journal article

C2 - 28539452

AN - SCOPUS:85026328907

VL - 91

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 16

M1 - e02319-16

ER -