Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15 and CXCR6 as Viral Coreceptors
| Autor: | Simoy Goldstein, Nadeene E. Riddick, Fan Wu, Kenta Matsuda, Jason M. Brenchley, Ronald J. Plishka, Alicia Buckler-White, Robert M. Goeken, Ilnour Ourmanov, Sonya Whitted, Vanessa M. Hirsch |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
animal diseases viruses Immunology CCR5 receptor antagonist Biology medicine.disease_cause Virus Replication Microbiology Peripheral blood mononuclear cell Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Virology Chlorocebus aethiops medicine Animals Lymphocytes Cells Cultured Maraviroc virus diseases Simian immunodeficiency virus Virus Internalization In vitro Virus-Cell Interactions 030104 developmental biology chemistry Viral replication Insect Science Receptors Virus Receptors Chemokine Simian Immunodeficiency Virus African Green Monkey 030215 immunology |
| Popis: | African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo , while human-derived CXCR6 and GPR15 also appear to be used in vitro . However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo . In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4 + T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4 + T cells and are potential alternative coreceptors for SIVagm use in vivo . These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals. IMPORTANCE African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo , other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro . In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo , since their mRNAs were detected in AGM memory CD4 + T cells, the preferred target cells of SIV. |
| Databáze: | OpenAIRE |
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