Potent restriction of HIV-1 and SIVmac239 Replication by African Green Monkey TRIM5α

Retrovirology

David E Ott¹  Claes Ohlen¹  Gregory Q Del Prete¹  Victor I Ayala¹  Sumiti Jain¹  Matthew T Trivett¹  Lori V Coren¹ 

[1] AIDS and Cancer Virus Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick 21702, MD, USA

关键词: Cumulative restriction;    Restriction factor;    TRIM5α;    SIV;    HIV;   

Others  :  1131915
DOI  :  10.1186/s12977-015-0137-9

 received in 2014-10-16, accepted in 2015-01-08,  发布年份 2015

【 摘 要 】

Background

The TRIM5α protein is a principal restriction factor that contributes to an HIV-1 replication block in rhesus macaque CD4⁺ T cells by preventing reverse transcription. HIV-1 restriction is induced in human CD4⁺ T cells by expression of rhesus TRIM5α as well as those of other old world monkeys. While TRIM5α restriction has been extensively studied in single-round infection assays, fewer studies have examined restriction after extended viral replication.

Results

To examine TRIM5α restriction of replication, we studied the ability of TRIM5α proteins from African green monkey (AgmTRIM5α) and gorilla (gorTRIM5α) to restrict HIV-1 and SIV_mac239 replication. These xenogeneic TRIM5α genes were transduced into human Jurkat-CCR5 cells (JR5), which were then exposed to HIV-1 or SIV_mac239. In our single-round infection assays, AgmTRIM5α showed a relatively modest 4- to 10-fold restriction of HIV-1 and SIV_mac239, while gorTRIM5α produced a 2- and 3-fold restriction of HIV-1 and SIV_mac239, respectively, consistent with the majority of previously published single-round studies. To assess the impact of these modest effects on infection, we tested restriction in replication systems initiated with either cell-free or cell-to-cell challenges. AgmTRIM5α powerfully restricted both HIV-1 and SIV_mac239 replication 14 days after cell-free infection, with a ≥ 3-log effect. Moreover, expression of AgmTRIM5α restricted HIV-1 and SIV_mac239 replication by 2-logs when co-cultured with infected JR5 cells for 12 days. In contrast, neither expression of gorTRIM5α nor rhesus TRIM5α induced significant resistance when co-cultured with infected cells. Follow up experiments showed that the observed differences between replication and infection were not due to assembly defects as xenogeneic TRIM5α expression had no effect on either virion production or specific infectivity.

Conclusions

Our results indicate that AgmTRIM5α has a much greater effect on extended replication than on any single infection event, suggesting that AgmTRIM5α restriction acts cumulatively, building up over many rounds of replication. Furthermore, AgmTRIM5α was able to potently restrict both HIV-1 and SIV replication in a cell-to-cell infection challenge. Thus, AgmTRIM5α is unique among the TRIM5α species tested to date, being able to restrict even at the high multiplicities of infection presented by mixed culture with nonrestrictive infected cells.

【 授权许可】

   
2015 Coren et al.; licensee BioMed Central.

【 图 表 】

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