Dimeric RNA Recognition Regulates HIV-1 Genome Packaging

PLoS Pathogens

Robert J. Gorelick¹  Ferri Soheilian²  Kunio Nagashima²  Wei-Shau Hu³  Kari A. Dilley³  Olga A. Nikolaitchik³  Vinay K. Pathak³  S.-H. Sheldon Tai³  William Fu⁴  Roger G. Ptak⁴ 

[1] AIDS and Cancer Virology Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America;Electron Microscopy Laboratory, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America;HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland, United States of America;Southern Research Institute, Frederick, Maryland, United States of America

关键词: HIV-1;    Virions;    Viral genomics;    Dimers (Chemical physics);    Genomic signal processing;    RNA viruses;    RNA structure;    Viral packaging;   

DOI  :  10.1371/journal.ppat.1003249

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

How retroviruses regulate the amount of RNA genome packaged into each virion has remained a long-standing question. Our previous study showed that most HIV-1 particles contain two copies of viral RNA, indicating that the number of genomes packaged is tightly regulated. In this report, we examine the mechanism that controls the number of RNA genomes encapsidated into HIV-1 particles. We hypothesize that HIV-1 regulates genome packaging by either the mass or copy number of the viral RNA. These two distinct mechanisms predict different outcomes when the genome size deviates significantly from that of wild type. Regulation by RNA mass would result in multiple copies of a small genome or one copy of a large genome being packaged, whereas regulation by copy number would result in two copies of a genome being packaged independent of size. To distinguish between these two hypotheses, we examined the packaging of viral RNA that was larger (≈17 kb) or smaller (≈3 kb) than that of wild-type HIV-1 (≈9 kb) and found that most particles packaged two copies of the viral genome regardless of whether they were 17 kb or 3 kb. Therefore, HIV-1 regulates RNA genome encapsidation not by the mass of RNA but by packaging two copies of RNA. To further explore the mechanism that governs this regulation, we examined the packaging of viral RNAs containing two packaging signals that can form intermolecular dimers or intramolecular dimers (self-dimers) and found that one self-dimer is packaged. Therefore, HIV-1 recognizes one dimeric RNA instead of two copies of RNA. Our findings reveal that dimeric RNA recognition is the key mechanism that regulates HIV-1 genome encapsidation and provide insights into a critical step in the generation of infectious viruses.

【 授权许可】

CC BY