CXCR6-Mediated Simian Immunodeficiency Virus SIVagmSab Entry into Sabaeus African Green Monkey Lymphocytes Implicates Widespread Use of Non-CCR5 Pathways in Natural Host Infections
| Autor: | Cristian Apetrei, Katherine S. Wetzel, Yanjie Yi, Sarah T. C. Elliott, Beatrice Jacquelin, Beatrice H. Hahn, Dino C. Romero, Ronald G. Collman, Ivona Pandrea, Michaela Müller-Trutwin |
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| Přispěvatelé: | University of Pennsylvania [Philadelphia], HIV, Inflammation et persistance, Institut Pasteur [Paris], University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), This work was funded by NIH grants R56-AI091516 and R01-MH06119 (R.G.C.), 2T32AI007632 (K.S.W.), R37-AI050529 (B.H.H.), and R01HL117715 (C.A. and I.P.). We also acknowledge assistance from multiple cores of the Penn Center for AIDS Research (P30-AI045008)., We thank F. Bibollet-Ruche, R. Warrier, and G. Learn for valuable advice and S. Bryan and F. Shaheen for technical assistance., University of Pennsylvania, HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes MESH: Sequence Analysis DNA Lymphocyte viruses MESH: Virus Internalization [SDV]Life Sciences [q-bio] Simian Acquired Immunodeficiency Syndrome MESH: Receptors CCR6 MESH: Receptors CCR5 medicine.disease_cause 0302 clinical medicine Viral Envelope Proteins Chlorocebus aethiops natural host MESH: Animals Lymphocytes Cloning Molecular MESH: Phylogeny Immunodeficiency Phylogeny tropism virus diseases MESH: CD4-Positive T-Lymphocytes coreceptor 3. Good health medicine.anatomical_structure Host-Pathogen Interactions [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology Receptors Virus MESH: Simian Acquired Immunodeficiency Syndrome Viral load Receptors CCR6 simian immunodeficiency virus Receptors CCR5 T cell Immunology MESH: Simian Immunodeficiency Virus [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Microbiology 03 medical and health sciences Virology medicine Animals MESH: Cloning Molecular Tropism MESH: Host-Pathogen Interactions Sequence Analysis DNA Simian immunodeficiency virus Virus Internalization medicine.disease MESH: Receptors Virus MESH: Cercopithecus aethiops CXCR6 African green monkey Viral Tropism 030104 developmental biology Viral replication Insect Science MESH: Viral Envelope Proteins Pathogenesis and Immunity MESH: Lymphocytes African Green Monkey MESH: Viral Tropism 030215 immunology |
| Zdroj: | Journal of Virology Journal of Virology, American Society for Microbiology, 2017, 91 (4), pp.e01626-16. ⟨10.1128/jvi.01626-16⟩ Journal of Virology, 2017, 91 (4), pp.e01626-16. ⟨10.1128/jvi.01626-16⟩ |
| ISSN: | 0022-538X 1098-5514 |
| DOI: | 10.1128/jvi.01626-16⟩ |
| Popis: | African green monkeys (AGM) and sooty mangabeys (SM) are well-studied natural hosts of simian immunodeficiency virus (SIV) that do not progress to AIDS when infected with their species-specific viruses. Natural hosts of SIV express very low levels of the canonical entry coreceptor CCR5, and recent studies have shown that CCR5 is dispensable for SIV infection of SM in vivo and that blocking of CCR5 does not prevent ex vivo infection of peripheral blood mononuclear cells (PBMC) from SM or vervet AGM. In both hosts, CXCR6 is an efficient entry pathway in vitro . Here we investigated the use of species-matched CXCR6 and other alternative coreceptors by SIVagmSab, which infects sabaeus AGM. We cloned sabaeus CD4 and 10 candidate coreceptors. Species-matched CXCR6, CCR5, and GPR15 mediated robust entry into transfected cells by pseudotypes carrying SIVagmSab92018ivTF Env, with lower-level entry through GPR1 and APJ. We cloned genetically divergent env genes from the plasma of two wild-infected sabaeus AGM and found similar patterns of coreceptor use. Titration experiments showed that CXCR6 and CCR5 were more efficient than other coreceptors when tested at limiting CD4/coreceptor levels. Finally, blocking of CXCR6 with its ligand CXCL16 significantly inhibited SIVagmSab replication in sabaeus PBMC and had a greater impact than did the CCR5 blocker maraviroc, confirming the use of CXCR6 in primary lymphocyte infection. These data suggest a new paradigm for SIV infection of natural host species, whereby a shared outcome of virus-host coevolution is the use of CXCR6 or other alternative coreceptors for entry, which may direct SIV toward CD4 + T cell subsets and anatomical sites that support viral replication without disrupting immune homeostasis and function. IMPORTANCE Natural hosts of SIV do not progress to AIDS, in stark contrast to pathogenic human immunodeficiency virus type 1 (HIV-1)-human and SIVmac-macaque infections. Identifying how natural hosts avoid immunodeficiency can elucidate key mechanisms of pathogenesis. It is known that despite high viral loads, natural hosts have a low frequency of CD4 + cells expressing the SIV coreceptor CCR5. In this study, we demonstrate the efficient use of the coreceptor CXCR6 by SIVagmSab to infect sabaeus African green monkey lymphocytes. In conjunction with studies of SIVsmm, which infects sooty mangabeys, and SIVagmVer, which infects vervet monkeys, our data suggest a unifying model whereby in natural hosts, in which the CCR5 expression level is low, the use of CXCR6 or other coreceptors to mediate infection may target SIV toward distinct cell populations that are able to support high-level viral replication without causing a loss of CD4 + T cell homeostasis and lymphoid tissue damage that lead to AIDS in HIV-1 and SIVmac infections. |
| Databáze: | OpenAIRE |
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