In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis
Simian immunodeficiency virus native to sooty mangabeys (SIVsm) is believed to have given rise to HIV-2 through cross-species transmission and evolution in the human. SIVmac239 and SIVB670, pathogenic to macaques, and SIVhu, isolated from an accidental human infection, also have origins in SIVsm. Wi...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Virology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fviro.2021.813606/full |
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| author | James Z. Curlin James Z. Curlin Kimberly Schmitt Leila Remling-Mulder Ryan V. Moriarty John J. Baczenas Kelly Goff Shelby O'Connor Mark Stenglein Preston A. Marx Preston A. Marx Ramesh Akkina |
| author_facet | James Z. Curlin James Z. Curlin Kimberly Schmitt Leila Remling-Mulder Ryan V. Moriarty John J. Baczenas Kelly Goff Shelby O'Connor Mark Stenglein Preston A. Marx Preston A. Marx Ramesh Akkina |
| author_sort | James Z. Curlin |
| collection | DOAJ |
| description | Simian immunodeficiency virus native to sooty mangabeys (SIVsm) is believed to have given rise to HIV-2 through cross-species transmission and evolution in the human. SIVmac239 and SIVB670, pathogenic to macaques, and SIVhu, isolated from an accidental human infection, also have origins in SIVsm. With their common ancestral lineage as that of HIV-2 from the progenitor SIVsm, but with different passage history in different hosts, they provide a unique opportunity to evaluate cross-species transmission to a new host and their adaptation/evolution both in terms of potential genetic and phenotypic changes. Using humanized mice with a transplanted human system, we evaluated in vivo replication kinetics, CD4+ T cell dynamics and genetic adaptive changes during serial passage with a goal to understand their evolution under human selective immune pressure. All the three viruses readily infected hu-mice causing chronic viremia. While SIVmac and SIVB670 caused CD4+ T cell depletion during sequential passaging, SIVhu with a deletion in nef gene was found to be less pathogenic. Deep sequencing of the genomes of these viruses isolated at different times revealed numerous adaptive mutations of significance that increased in frequency during sequential passages. The ability of these viruses to infect and replicate in humanized mice provides a new small animal model to study SIVs in vivo in addition to more expensive macaques. Since SIVmac and related viruses have been indispensable in many areas of HIV pathogenesis, therapeutics and cure research, availability of this small animal hu-mouse model that is susceptible to both SIV and HIV viruses is likely to open novel avenues of investigation for comparative studies using the same host. |
| first_indexed | 2024-12-22T20:08:55Z |
| format | Article |
| id | doaj.art-d97621aa07f743bab0ffc72464e7ee60 |
| institution | Directory Open Access Journal |
| issn | 2673-818X |
| language | English |
| last_indexed | 2024-12-22T20:08:55Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Virology |
| spelling | doaj.art-d97621aa07f743bab0ffc72464e7ee602022-12-21T18:14:05ZengFrontiers Media S.A.Frontiers in Virology2673-818X2021-12-01110.3389/fviro.2021.813606813606In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 GenesisJames Z. Curlin0James Z. Curlin1Kimberly Schmitt2Leila Remling-Mulder3Ryan V. Moriarty4John J. Baczenas5Kelly Goff6Shelby O'Connor7Mark Stenglein8Preston A. Marx9Preston A. Marx10Ramesh Akkina11Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesAntiviral Discovery, Evaluation and Application Research (ADEAR) Training Program, Department of Medicine, University of Colorado, Aurora, CO, United StatesDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United StatesDepartment of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United StatesDepartment of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, United StatesDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesDepartment of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United StatesTulane National Primate Research Center, Covington, LA, United StatesDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesSimian immunodeficiency virus native to sooty mangabeys (SIVsm) is believed to have given rise to HIV-2 through cross-species transmission and evolution in the human. SIVmac239 and SIVB670, pathogenic to macaques, and SIVhu, isolated from an accidental human infection, also have origins in SIVsm. With their common ancestral lineage as that of HIV-2 from the progenitor SIVsm, but with different passage history in different hosts, they provide a unique opportunity to evaluate cross-species transmission to a new host and their adaptation/evolution both in terms of potential genetic and phenotypic changes. Using humanized mice with a transplanted human system, we evaluated in vivo replication kinetics, CD4+ T cell dynamics and genetic adaptive changes during serial passage with a goal to understand their evolution under human selective immune pressure. All the three viruses readily infected hu-mice causing chronic viremia. While SIVmac and SIVB670 caused CD4+ T cell depletion during sequential passaging, SIVhu with a deletion in nef gene was found to be less pathogenic. Deep sequencing of the genomes of these viruses isolated at different times revealed numerous adaptive mutations of significance that increased in frequency during sequential passages. The ability of these viruses to infect and replicate in humanized mice provides a new small animal model to study SIVs in vivo in addition to more expensive macaques. Since SIVmac and related viruses have been indispensable in many areas of HIV pathogenesis, therapeutics and cure research, availability of this small animal hu-mouse model that is susceptible to both SIV and HIV viruses is likely to open novel avenues of investigation for comparative studies using the same host.https://www.frontiersin.org/articles/10.3389/fviro.2021.813606/fullHIV origins and evolution from SIVSIV cross-species transmissiona dual purpose humanized mouse model for HIV and SIV researchSIVmac and SIVB670 pathogenesis and evolution in humanized miceviral adaptive changes and evolutionSIV evolution into HIV-2 |
| spellingShingle | James Z. Curlin James Z. Curlin Kimberly Schmitt Leila Remling-Mulder Ryan V. Moriarty John J. Baczenas Kelly Goff Shelby O'Connor Mark Stenglein Preston A. Marx Preston A. Marx Ramesh Akkina In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis Frontiers in Virology HIV origins and evolution from SIV SIV cross-species transmission a dual purpose humanized mouse model for HIV and SIV research SIVmac and SIVB670 pathogenesis and evolution in humanized mice viral adaptive changes and evolution SIV evolution into HIV-2 |
| title | In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis |
| title_full | In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis |
| title_fullStr | In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis |
| title_full_unstemmed | In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis |
| title_short | In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis |
| title_sort | in vivo infection dynamics and human adaptive changes of sivsm derived viral siblings sivmac239 sivb670 and sivhu in humanized mice as a paralog of hiv 2 genesis |
| topic | HIV origins and evolution from SIV SIV cross-species transmission a dual purpose humanized mouse model for HIV and SIV research SIVmac and SIVB670 pathogenesis and evolution in humanized mice viral adaptive changes and evolution SIV evolution into HIV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2021.813606/full |
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