Pathogenic infection of Macaca nemestrina with a CCR5-tropic subtype-C simian-human immunodeficiency virus.
BACKGROUND
Although pig-tailed macaques (Macaca nemestrina) have been used in AIDS research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (Macaca mulatta). Similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (SIV), but less so for chimeric simian-human immunodeficiency viruses (SHIV), although the latter have been widely used in HIV vaccine studies. Here, we report the consequences of intrarectal infection with a CCR5-tropic clade C SHIV-1157ipd3N4 in pig-tailed macaques.


RESULTS
Plasma and cell-associated virus was detectable in peripheral blood and intestinal tissues of all four pig-tailed macaques following intrarectal inoculation with SHIV-1157ipd3N4. We also observed a rapid and irreversible loss of CD4+ T cells at multiple mucosal sites, resulting in a marked decrease of CD4:CD8 T cell ratios 0.5-4 weeks after inoculation. This depletion targeted subsets of CD4+ T cells expressing the CCR5 coreceptor and having a CD28-CD95+ effector memory phenotype, consistent with the R5-tropism of SHIV-1157ipd3N4. All three animals that were studied beyond the acute phase seroconverted as early as week 4, with two developing cross-clade neutralizing antibody responses by week 24. These two animals also demonstrated persistent plasma viremia for >48 weeks. One of these animals developed AIDS, as shown by peripheral blood CD4+ T-cell depletion starting at 20 weeks post inoculation.


CONCLUSIONS
These findings indicate that SHIV-1157ipd3N4-induced pathogenesis in pig-tailed macaques followed a similar course as SIV-infected rhesus macaques. Thus, R5 SHIV-C-infection of pig-tailed macaques could provide a useful and relevant model for AIDS vaccine and pathogenesis research.
Ho
On
O
Department of Pharmaceutics, University of Washington, Seattle, 98195, USA. onh@bart.rprc.washington.edu
Larsen
Kay
K
Polacino
Patricia
P
Li
Yun
Y
Anderson
David
D
Song
Ruijiang
R
Ruprecht
Ruth M
RM
Hu
Shiu-Lok
SL
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001769:Blood / Q000821:virology; D018106:CD28 Antigens / Q000032:analysis; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D006678:HIV / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D007413:Intestinal Mucosa / Q000821:virology; D016131:Lymphocyte Subsets / Q000276:immunology; D008254:Macaca nemestrina / Q000821:virology*; D009500:Neutralization Tests; D019713:Receptors, CCR5 / Q000032:analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D019014:fas Receptor
D000914:Antibodies, Viral; D018106:CD28 Antigens; D019713:Receptors, CCR5; D019014:fas Receptor