The human antiviral factor TRIM11 is under the regulation of HIV-1 Vpr

Ting Yuan; Weitong Yao; Fang Huang; Binlian Sun; Rongge Yang

doi:10.1371/journal.pone.0104269

The human antiviral factor TRIM11 is under the regulation of HIV-1 Vpr

PLoS One. 2014 Aug 8;9(8):e104269. doi: 10.1371/journal.pone.0104269. eCollection 2014.

Authors

Ting Yuan¹, Weitong Yao¹, Fang Huang¹, Binlian Sun¹, Rongge Yang¹

Affiliation

¹ Research Group of HIV Molecular Epidemiology and Virology, Center for Emerging Infectious Diseases, The State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, The People's Republic of China.

Abstract

TRIM11 has been reported to be able to restrict HIV-1 replication, but the detailed aspects of the interfering mechanisms remain unclear. In this study, we demonstrated that TRIM11 mainly suppressed the early steps of HIV-1 transduction, resulting in decreased reverse transcripts. Additionally, we found that TRIM11 could inhibit HIV-1 long terminal repeat (LTR) activity, which may be related to its inhibitory effects on NF-κB. Deletion mutant experiments showed that the RING domain of TRIM11 was indispensable in inhibiting the early steps of HIV-1 transduction but was dispensable in decreasing NF-κB and LTR activities. Moreover, we found that low levels of Vpr decreased TRIM11 protein levels, while high levels increased them, and these regulations were independent of the VprBP-associated proteasome machinery. These results suggest that the antiviral factor TRIM11 is indirectly regulated by HIV-1 Vpr through unknown mechanisms and that the concentration of Vpr is essential to these processes. Thus, our work confirms TRIM11 as a host cellular factor that interferes with the early steps of HIV-1 replication and provides a connection between viral protein and host antiviral factors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Primers / genetics
Genetic Vectors / genetics
HEK293 Cells
HIV Long Terminal Repeat / physiology
Humans
Immunoprecipitation
Luciferases
RNA, Small Interfering / genetics
Real-Time Polymerase Chain Reaction
Tripartite Motif Proteins
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism*
Ubiquitin-Protein Ligases / physiology
Virus Internalization*
Virus Replication / physiology*
vpr Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

DNA Primers
RNA, Small Interfering
Tripartite Motif Proteins
vpr Gene Products, Human Immunodeficiency Virus
vpr protein, Human immunodeficiency virus 1
Luciferases
TRIM11 protein, human
Ubiquitin-Protein Ligases

Grants and funding

This study was supported by the Key National Science and Technology Program in the twelfth Five-Year Period (Grant 2012ZX10001-006) and grants from the International Science & Technology Cooperation Program of China (2011DFA31030) and Deutsche Forschungsgemeinschaft (SFB/Transregio TRR60). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.