Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages
Rhesus macaques can be readily infected with chimeric simian-human immunodeficiency viruses (SHIV) as a suitable virus challenge system for testing the efficacy of HIV vaccines. Three Chinese-origin rhesus macaques (ChRM) were inoculated intravenously (IV) with SHIVC109P4 in a rapid serial in vivo p...
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| Format: | Article |
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MDPI AG
2021-03-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/13/3/397 |
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| author | Gerald K. Chege Craig H. Adams Alana T. Keyser Valerie Bekker Lynn Morris Francois J. Villinger Anna-Lise Williamson Rosamund E. Chapman |
| author_facet | Gerald K. Chege Craig H. Adams Alana T. Keyser Valerie Bekker Lynn Morris Francois J. Villinger Anna-Lise Williamson Rosamund E. Chapman |
| author_sort | Gerald K. Chege |
| collection | DOAJ |
| description | Rhesus macaques can be readily infected with chimeric simian-human immunodeficiency viruses (SHIV) as a suitable virus challenge system for testing the efficacy of HIV vaccines. Three Chinese-origin rhesus macaques (ChRM) were inoculated intravenously (IV) with SHIVC109P4 in a rapid serial in vivo passage. SHIV recovered from the peripheral blood of the final ChRM was used to generate a ChRM-adapted virus challenge stock. This stock was titrated for the intrarectal route (IR) in 8 ChRMs using undiluted, 1:10 or 1:100 dilutions, to determine a suitable dose for use in future vaccine efficacy testing via repeated low-dose IR challenges. All 11 ChRMs were successfully infected, reaching similar median peak viraemias at 1–2 weeks post inoculation but undetectable levels by 8 weeks post inoculation. T-cell responses were detected in all animals and Tier 1 neutralizing antibodies (Nab) developed in 10 of 11 infected ChRMs. All ChRMs remained healthy and maintained normal CD4<sup>+</sup> T cell counts. Sequence analyses showed >98% amino acid identity between the original inoculum and virus recovered at peak viraemia indicating only minimal changes in the env gene. Thus, while replication is limited over time, our adapted SHIV can be used to test for protection of virus acquisition in ChRMs. |
| first_indexed | 2024-03-09T05:55:02Z |
| format | Article |
| id | doaj.art-2b7cb80af5e9420aa779805dc59be700 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T05:55:02Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-2b7cb80af5e9420aa779805dc59be7002023-12-03T12:14:06ZengMDPI AGViruses1999-49152021-03-0113339710.3390/v13030397Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial PassagesGerald K. Chege0Craig H. Adams1Alana T. Keyser2Valerie Bekker3Lynn Morris4Francois J. Villinger5Anna-Lise Williamson6Rosamund E. Chapman7Primate Unit and Delft Animal Centre, Centre and Platform Office, South African Medical Research Council, Parow Valley, 7505 Cape Town, South AfricaDivision of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South AfricaDivision of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South AfricaCentre for HIV and STIs, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Sandringham, 2131 Johannesburg, South AfricaCentre for HIV and STIs, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Sandringham, 2131 Johannesburg, South AfricaNew Iberia Research Center, University of Louisiana, Louisiana, LA 70560, USADivision of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South AfricaDivision of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South AfricaRhesus macaques can be readily infected with chimeric simian-human immunodeficiency viruses (SHIV) as a suitable virus challenge system for testing the efficacy of HIV vaccines. Three Chinese-origin rhesus macaques (ChRM) were inoculated intravenously (IV) with SHIVC109P4 in a rapid serial in vivo passage. SHIV recovered from the peripheral blood of the final ChRM was used to generate a ChRM-adapted virus challenge stock. This stock was titrated for the intrarectal route (IR) in 8 ChRMs using undiluted, 1:10 or 1:100 dilutions, to determine a suitable dose for use in future vaccine efficacy testing via repeated low-dose IR challenges. All 11 ChRMs were successfully infected, reaching similar median peak viraemias at 1–2 weeks post inoculation but undetectable levels by 8 weeks post inoculation. T-cell responses were detected in all animals and Tier 1 neutralizing antibodies (Nab) developed in 10 of 11 infected ChRMs. All ChRMs remained healthy and maintained normal CD4<sup>+</sup> T cell counts. Sequence analyses showed >98% amino acid identity between the original inoculum and virus recovered at peak viraemia indicating only minimal changes in the env gene. Thus, while replication is limited over time, our adapted SHIV can be used to test for protection of virus acquisition in ChRMs.https://www.mdpi.com/1999-4915/13/3/397SHIVsubtype CChinese rhesus macaques |
| spellingShingle | Gerald K. Chege Craig H. Adams Alana T. Keyser Valerie Bekker Lynn Morris Francois J. Villinger Anna-Lise Williamson Rosamund E. Chapman Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages Viruses SHIV subtype C Chinese rhesus macaques |
| title | Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages |
| title_full | Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages |
| title_fullStr | Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages |
| title_full_unstemmed | Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages |
| title_short | Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages |
| title_sort | infection of chinese rhesus monkeys with a subtype c shiv resulted in attenuated in vivo viral replication despite successful animal to animal serial passages |
| topic | SHIV subtype C Chinese rhesus macaques |
| url | https://www.mdpi.com/1999-4915/13/3/397 |
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