Replicative fitness and pathogenicity of primate lentiviruses in lymphoid tissue, primary human and chimpanzee cells: relation to possible jumps to humansResearch in context
Denis M. Tebit,
Gabrielle Nickel,
Richard Gibson,
Myriam Rodriguez,
Nicolas J. Hathaway,
Katie Bain,
Angel L. Reyes-Rodriguez,
Pascal Ondoa,
Jonathan L. Heeney,
Yue Li,
Jennifer Bongorno,
David Canaday,
David McDonald,
Jeffrey A. Bailey,
Eric J. Arts
Affiliations
Denis M. Tebit
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Global Biomed Scientific, LLC, P.O. Box 2368, Forest, VA, USA
Gabrielle Nickel
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
Richard Gibson
Department of Microbiology and Immunology, Western University, Ontario, Canada
Myriam Rodriguez
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
Nicolas J. Hathaway
Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA
Katie Bain
Department of Microbiology and Immunology, Western University, Ontario, Canada
Angel L. Reyes-Rodriguez
Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Pascal Ondoa
African Society for Laboratory Medicine, Addis Ababa, Ethiopia; Department of Global Health, Institute of Global Health and Development, University of Amsterdam, Amsterdam, the Netherlands
Jonathan L. Heeney
Laboratory of Viral Zoonotics, Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
Yue Li
Department of Microbiology and Immunology, Western University, Ontario, Canada
Jennifer Bongorno
Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
David Canaday
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA
David McDonald
Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Jeffrey A. Bailey
Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA
Eric J. Arts
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA; Department of Microbiology and Immunology, Western University, Ontario, Canada; Corresponding author. 1151 Richmond St., Department of Microbiology and Immunology, Western University, Ontario, N6A 3K7, Canada.
Summary: Background: Simian immunodeficiency viruses (SIV) have been jumping between non-human primates in West/Central Africa for thousands of years and yet, the HIV-1 epidemic only originated from a primate lentivirus over 100 years ago. Methods: This study examined the replicative fitness, transmission, restriction, and cytopathogenicity of 22 primate lentiviruses in primary human lymphoid tissue and both primary human and chimpanzee peripheral blood mononuclear cells. Findings: Pairwise competitions revealed that SIV from chimpanzees (cpz) had the highest replicative fitness in human or chimpanzee peripheral blood mononuclear cells, even higher fitness than HIV-1 group M strains responsible for worldwide epidemic. The SIV strains belonging to the “HIV-2 lineage” (including SIVsmm, SIVmac, SIVagm) had the lowest replicative fitness. SIVcpz strains were less inhibited by human restriction factors than the “HIV-2 lineage” strains. SIVcpz efficiently replicated in human tonsillar tissue but did not deplete CD4+ T-cells, consistent with the slow or nonpathogenic disease observed in most chimpanzees. In contrast, HIV-1 isolates and SIV of the HIV-2 lineage were pathogenic to the human tonsillar tissue, almost independent of the level of virus replication. Interpretation: Of all primate lentiviruses, SIV from chimpanzees appears most capable of infecting and replicating in humans, establishing HIV-1. SIV from other Old World monkeys, e.g. the progenitor of HIV-2, replicate slowly in humans due in part to restriction factors. Nonetheless, many of these SIV strains were more pathogenic than SIVcpz. Either SIVcpz evolved into a more pathogenic virus while in humans or a rare SIVcpz, possibly extinct in chimpanzees, was pathogenic immediately following the jump into human. Funding: Support for this study to E.J.A. was provided by the NIH/NIAID R01 AI49170 and CIHR project grant 385787. Infrastructure support was provided by the NIH CFAR AI36219 and Canadian CFI/Ontario ORF 36287. Efforts of J.A.B. and N.J.H. was provided by NIH AI099473 and for D.H.C., by VA and NIH AI AI080313.
