Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle

PLoS Pathogens

Simran Khurana¹  James D. Stamos¹  Alix Warburton¹  Alison A. McBride¹  Wesley H. Stepp¹ 

[1] Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: Viral replication;    DNA replication;    Cell differentiation;    HPV-31;    Small interfering RNAs;    Chromatin;    HPV-16;    Keratinocytes;   

DOI  :  10.1371/journal.ppat.1006660

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

We have shown previously that Sp100 (a component of the ND10 nuclear body) represses transcription, replication and establishment of incoming human papillomavirus (HPV) DNA in the early stages of infection. In this follow up study, we show that Sp100 does not substantially regulate viral infection in the maintenance phase, however at late stages of infection Sp100 interacts with amplifying viral genomes to repress viral processes. We find that Sp100 localizes to HPV16 replication foci generated in primary keratinocytes, to HPV31 replication foci that form in differentiated cells, and to HPV16 replication foci in CIN 1 cervical biopsies. To analyze this further, Sp100 was down regulated by siRNA treatment of differentiating HPV31 containing cells and levels of viral transcription and replication were assessed. This revealed that Sp100 represses viral transcription and replication in differentiated cells. Analysis of Sp100 binding to viral chromatin showed that Sp100 bound across the viral genome, and that binding increased at late stages of infection. Therefore, Sp100 represses the HPV life cycle at both early and late stages of infection.

【 授权许可】

CC BY