A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART
Selection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/8/1609 |
| _version_ | 1797521797715853312 |
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| author | Megan A. O’Connor Paul V. Munson Sandra E. Dross Hillary C. Tunggal Thomas B. Lewis Jessica Osborn Christopher W. Peterson Meei-Li W. Huang Cassandra Moats Jeremy Smedley Keith R. Jerome Hans-Peter Kiem Kenneth C. Bagley James I. Mullins Deborah Heydenburg Fuller |
| author_facet | Megan A. O’Connor Paul V. Munson Sandra E. Dross Hillary C. Tunggal Thomas B. Lewis Jessica Osborn Christopher W. Peterson Meei-Li W. Huang Cassandra Moats Jeremy Smedley Keith R. Jerome Hans-Peter Kiem Kenneth C. Bagley James I. Mullins Deborah Heydenburg Fuller |
| author_sort | Megan A. O’Connor |
| collection | DOAJ |
| description | Selection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the NHP model for AIDS could influence outcomes in studies investigating interventions. Previously, in rhesus macaques (RMs) we showed that maintenance of mucosal Th17/Treg homeostasis during SIV infection correlated with a better virological response to cART. Here, in RMs we compared viral kinetics and dysregulation of gut homeostasis, defined by T cell subset disruption, during highly pathogenic SIVΔB670 compared to SHIV-1157ipd3N4 infection. SHIV infection resulted in lower acute viremia and less disruption to gut CD4 T-cell homeostasis. Additionally, 24/24 SHIV-infected versus 10/19 SIV-infected animals had sustained viral suppression <100 copies/mL of plasma after 5 months of cART. Significantly, the more profound viral suppression during cART in a subset of SIV and all SHIV-infected RMs corresponded with less gut immune dysregulation during acute SIV/SHIV infection, defined by maintenance of the Th17/Treg ratio. These results highlight significant differences in viral control during cART and gut dysregulation in NHP AIDS models and suggest that selection of a model may impact the evaluation of candidate therapeutic interventions for HIV treatment and cure strategies. |
| first_indexed | 2024-03-10T08:17:40Z |
| format | Article |
| id | doaj.art-869a7204016a440a9ee51fd5e61ea6cb |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T08:17:40Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-869a7204016a440a9ee51fd5e61ea6cb2023-11-22T10:12:04ZengMDPI AGViruses1999-49152021-08-01138160910.3390/v13081609A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cARTMegan A. O’Connor0Paul V. Munson1Sandra E. Dross2Hillary C. Tunggal3Thomas B. Lewis4Jessica Osborn5Christopher W. Peterson6Meei-Li W. Huang7Cassandra Moats8Jeremy Smedley9Keith R. Jerome10Hans-Peter Kiem11Kenneth C. Bagley12James I. Mullins13Deborah Heydenburg Fuller14Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USADepartment of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USADepartment of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USADepartment of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USADepartment of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USADepartment of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USAStem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USADepartment of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USAWashington National Primate Research Center, 1705 NE Pacific Street, Seattle, WA 98195, USAWashington National Primate Research Center, 1705 NE Pacific Street, Seattle, WA 98195, USAStem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USAStem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USAProfectus Biosciences Inc., 6411 Beckley Street, Baltimore, MD 21224, USADepartment of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USADepartment of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USASelection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the NHP model for AIDS could influence outcomes in studies investigating interventions. Previously, in rhesus macaques (RMs) we showed that maintenance of mucosal Th17/Treg homeostasis during SIV infection correlated with a better virological response to cART. Here, in RMs we compared viral kinetics and dysregulation of gut homeostasis, defined by T cell subset disruption, during highly pathogenic SIVΔB670 compared to SHIV-1157ipd3N4 infection. SHIV infection resulted in lower acute viremia and less disruption to gut CD4 T-cell homeostasis. Additionally, 24/24 SHIV-infected versus 10/19 SIV-infected animals had sustained viral suppression <100 copies/mL of plasma after 5 months of cART. Significantly, the more profound viral suppression during cART in a subset of SIV and all SHIV-infected RMs corresponded with less gut immune dysregulation during acute SIV/SHIV infection, defined by maintenance of the Th17/Treg ratio. These results highlight significant differences in viral control during cART and gut dysregulation in NHP AIDS models and suggest that selection of a model may impact the evaluation of candidate therapeutic interventions for HIV treatment and cure strategies.https://www.mdpi.com/1999-4915/13/8/1609non-human primate (NHP)SHIVSIVcARTcolonT helper 17 (Th17) |
| spellingShingle | Megan A. O’Connor Paul V. Munson Sandra E. Dross Hillary C. Tunggal Thomas B. Lewis Jessica Osborn Christopher W. Peterson Meei-Li W. Huang Cassandra Moats Jeremy Smedley Keith R. Jerome Hans-Peter Kiem Kenneth C. Bagley James I. Mullins Deborah Heydenburg Fuller A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART Viruses non-human primate (NHP) SHIV SIV cART colon T helper 17 (Th17) |
| title | A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART |
| title_full | A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART |
| title_fullStr | A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART |
| title_full_unstemmed | A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART |
| title_short | A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART |
| title_sort | gut reaction to siv and shiv infection lower dysregulation of mucosal t cells during acute infection is associated with greater viral suppression during cart |
| topic | non-human primate (NHP) SHIV SIV cART colon T helper 17 (Th17) |
| url | https://www.mdpi.com/1999-4915/13/8/1609 |
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