SIVagm from African green monkeys can use non-CCR5 entry pathways in vitro and ex vivo

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Authors

• NE Riddick
• RM Goeken
• S Whitted
• JM Brenchley
• VM Hirsch

Abstract

Background: CCR5 has been described as a primary coreceptor for SIV. A recent study identified SIV-infected sooty mangabeys that were genetically CCR5-deficient. This finding suggests that the use of non-CCR5 entry pathways in vivo may be a feature of SIV strains found in natural hosts. We sought to further examine the role of CCR5 as an entry coreceptor for SIV derived from another natural host species, the vervet African green monkey (AGM). We also examined the ability of AGM-derived alternative coreceptors to serve as potential entry coreceptors for SIVagm. Results: SIVagmVer90 efficiently replicated in AGM PBMC in the absence and presence of maraviroc, which suggests the use of non-CCR5 entry pathways. In vitro infections revealed that reporter viruses carrying various SIVagm envelopes, including transmitted/founder (T/F) envelopes, utilized AGM-derived GPR15 and CXCR6, in addition to CCR5, for entry into target cells. AGM PBMC were sorted into various cell subsets to determine if GPR15 and/or CXCR6 are expressed on CD4 lymphocytes. CCR5, GPR15 and CXCR6 mRNA were detected in the CD4 memory subset. Conclusions: These results indicate that SIVagm viruses can utilize non-CCR5 entry pathways ex vivo, and various SIVagm envelopes, including T/F envelopes, utilized GPR15 and CXCR6 for entry into target cells. Detection of GPR15 and CXCR6 mRNA in AGM CD4 lymphocytes supports the notion that these alternative coreceptors may serve as potential SIV entry coreceptors. These data suggest that the use of non-CCR5 entry pathways may be a common feature to SIV derived from natural hosts.

Scientific Focus Area: Microbiology and Infectious Diseases

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