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

被引：1

作者：

Chege, Gerald K. ^{[1
,2
,3
]}

Adams, Craig H. ^{[3
]}

Keyser, Alana T. ^{[3
]}

Bekker, Valerie ^{[4
]}

Morris, Lynn ^{[4
,5
]}

Villinger, Francois J. ^{[6
]}

Williamson, Anna-Lise ^{[3
]}

Chapman, Rosamund E. ^{[3
]}

机构：

[1] South African Med Res Council, Ctr & Platform Off, Primate Unit, ZA-7505 Cape Town, South Africa

[2] South African Med Res Council, Ctr & Platform Off, Delft Anim Ctr, ZA-7505 Cape Town, South Africa

[3] Univ Cape Town, Inst Infect Dis & Mol Med, Dept Pathol, Div Med Virol, ZA-7925 Cape Town, South Africa

[4] Natl Inst Communicable Dis, Ctr HIV & STIs, ZA-2131 Johannesburg, South Africa

[5] Univ Witwatersrand, Fac Hlth Sci, Antibody Immun Res Unit, ZA-2050 Johannesburg, South Africa

[6] Univ Louisiana, New Iberia Res Ctr, Louisiana, LA 70560 USA

来源：

VIRUSES-BASEL | 2021年 / 13卷 / 03期

基金：

新加坡国家研究基金会; 英国医学研究理事会;

关键词：

SHIV; subtype C; Chinese rhesus macaques; HUMAN-IMMUNODEFICIENCY-VIRUS; BOOSTS IMMUNE-RESPONSES; DISEASE PROGRESSION; CELL DEPLETION; CD4; BINDING; MACAQUES; HIV; VACCINE; TYPE-1; ORIGIN;

D O I：

10.3390/v13030397

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：19