Infection of Chinese Rhesus Monkeys with a Subtype C SHIV Resulted in Attenuated In Vivo Viral Replication Despite Successful Animal-to-Animal Serial Passages.

Autor: Chege GK; Primate Unit and Delft Animal Centre, Centre and Platform Office, South African Medical Research Council, Parow Valley, 7505 Cape Town, South Africa.; Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa., Adams CH; Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa., Keyser AT; Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa., Bekker V; Centre for HIV and STIs, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Sandringham, 2131 Johannesburg, South Africa., Morris L; Centre for HIV and STIs, National Institute for Communicable Diseases, a Division of the National Health Laboratory Service, Sandringham, 2131 Johannesburg, South Africa.; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Wits, 2050 Johannesburg, South Africa., Villinger FJ; New Iberia Research Center, University of Louisiana, Louisiana, LA 70560, USA., Williamson AL; Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa., Chapman RE; Division of Medical Virology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, 7925 Cape Town, South Africa.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2021 Mar 02; Vol. 13 (3). Date of Electronic Publication: 2021 Mar 02.
DOI: 10.3390/v13030397
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje