Secretion of Genome-Free Hepatitis B Virus – Single Strand Blocking Model for Virion Morphogenesis of Para-retrovirus

PLoS Pathogens

Xiaojun Ning¹  Susan Hafenstein¹  Laura Mentzer¹  David Nguyen¹  Christina Adams¹  Hyunwook Lee¹  Robert Ashley²  Jianming Hu² 

[1] Department of Microbiology and Immunology, The Penn State University College of Medicine, Hershey, Pennsylvania, United States of America;Division of Infectious Diseases, Department of Medicine, The Penn State University College of Medicine, Hershey, Pennsylvania, United States of America

关键词: Virions;    Viral packaging;    Nucleic acids;    Secretion;    Viral core;    Chimpanzees;    Viral nucleic acid;    Hepatitis B virus;   

DOI  :  10.1371/journal.ppat.1002255

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

As a para-retrovirus, hepatitis B virus (HBV) is an enveloped virus with a double-stranded (DS) DNA genome that is replicated by reverse transcription of an RNA intermediate, the pregenomic RNA or pgRNA. HBV assembly begins with the formation of an “immature” nucleocapsid (NC) incorporating pgRNA, which is converted via reverse transcription within the maturing NC to the DS DNA genome. Only the mature, DS DNA-containing NCs are enveloped and secreted as virions whereas immature NCs containing RNA or single-stranded (SS) DNA are not enveloped. The current model for selective virion morphogenesis postulates that accumulation of DS DNA within the NC induces a “maturation signal” that, in turn, triggers its envelopment and secretion. However, we have found, by careful quantification of viral DNA and NCs in HBV virions secreted in vitro and in vivo, that the vast majority of HBV virions (over 90%) contained no DNA at all, indicating that NCs with no genome were enveloped and secreted as empty virions (i.e., enveloped NCs with no DNA). Furthermore, viral mutants bearing mutations precluding any DNA synthesis secreted exclusively empty virions. Thus, viral DNA synthesis is not required for HBV virion morphogenesis. On the other hand, NCs containing RNA or SS DNA were excluded from virion formation. The secretion of DS DNA-containing as well as empty virions on one hand, and the lack of secretion of virions containing single-stranded (SS) DNA or RNA on the other, prompted us to propose an alternative, “Single Strand Blocking” model to explain selective HBV morphogenesis whereby SS nucleic acid within the NC negatively regulates NC envelopment, which is relieved upon second strand DNA synthesis.

【 授权许可】

CC BY