Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages
Gerald K. Chege,
Craig H. Adams,
Alana T. Keyser,
Valerie Bekker,
Lynn Morris,
Francois J. Villinger,
Anna-Lise Williamson,
Rosamund E. Chapman
Affiliations
Gerald K. Chege
Primate Unit and Delft Animal Centre, Centre and Platform Office, South African Medical Research Council, Parow Valley, 7505 Cape Town, South Africa
Craig H. Adams
Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa
Alana T. Keyser
Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa
Valerie Bekker
Centre for HIV and STIs, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Sandringham, 2131 Johannesburg, South Africa
Lynn Morris
Centre for HIV and STIs, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Sandringham, 2131 Johannesburg, South Africa
Francois J. Villinger
New Iberia Research Center, University of Louisiana, Louisiana, LA 70560, USA
Anna-Lise Williamson
Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa
Rosamund E. Chapman
Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa
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+ 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.
