Hongzhao Li1, Robert W Omange1, Chris Czarnecki2, Jorge F Correia-Pinto3, Jose Crecente-Campo3, Meika Richmond1, Lin Li1, Nancy Schultz-Darken4, Maria J Alonso3, James B Whitney5,6, Francis A Plummer1,2, Ma Luo1,2. 1. Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. 2. National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada. 3. CIMUS Research Institute, University of Santiago de Compostela, Santiago de Compostela, Spain. 4. Wisconsin National Primate Research Center, Madison, WI, USA. 5. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 6. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Abstract
BACKGROUND: Understanding natural HIV control may lead to new preventative or therapeutic strategies. Several protective major histocompatibility complex (MHC) genotypes were found in humans and rhesus macaques. Here, we report a simian immunodeficiency virus (SIV) controller MHC genotype in Mauritian cynomolgus macaques (MCMs). METHODS: Twelve MHC-genotyped MCMs were infected with SIVmac251 and monitored for viral loads and CD4+ T-cell counts. RESULTS: Two macaques with M3M4 genotype exhibited the lowest peak viral loads (log plasma SIV RNA copies/mL), nearly 3 logs lower than those in most macaques with other MHC haplotype combinations, and set point viral loads below the level of detection limit by RT-qPCR (<2 log RNA copies/mL). They maintained healthy CD4+ T-cell counts of >500 cells/μL blood, while CD4 counts in the vast majority of other macaques were below this level. CONCLUSIONS: The M3M4 MHC genotype may confer enhanced control of SIV replication in MCMs.
BACKGROUND: Understanding natural HIV control may lead to new preventative or therapeutic strategies. Several protective major histocompatibility complex (MHC) genotypes were found in humans and rhesus macaques. Here, we report a simian immunodeficiency virus (SIV) controller MHC genotype in Mauritian cynomolgus macaques (MCMs). METHODS: Twelve MHC-genotyped MCMs were infected with SIVmac251 and monitored for viral loads and CD4+ T-cell counts. RESULTS: Two macaques with M3M4 genotype exhibited the lowest peak viral loads (log plasma SIV RNA copies/mL), nearly 3 logs lower than those in most macaques with other MHC haplotype combinations, and set point viral loads below the level of detection limit by RT-qPCR (<2 log RNA copies/mL). They maintained healthy CD4+ T-cell counts of >500 cells/μL blood, while CD4 counts in the vast majority of other macaques were below this level. CONCLUSIONS: The M3M4 MHC genotype may confer enhanced control of SIV replication in MCMs.
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