Early divergence in neutrophil apoptosis between pathogenic and nonpathogenic simian immunodeficiency virus infections of nonhuman primates.
We used pathogenic and nonpathogenic simian models of SIV infection of Chinese and Indian rhesus macaque (RMs) and African green monkeys (AGMs), respectively, to investigate the relationship between polymorphonuclear neutrophil (PMN) death and the extent of viral replication and disease outcome. In this study, we showed that PMN death increased early during the acute phase of SIV infection in Chinese RMs and coincided with the peak of viral replication on day 14. The level of PMN death was significantly more severe in RMs that progressed more rapidly to AIDS and coincided with neutropenia. Neutropenia was also observed in Indian RMs and was higher in non-Mamu-A*01 compared with Mamu-A*01 animals. In stark contrast, no changes in the levels of PMN death were observed in the nonpathogenic model of SIVagm-sab (sabaeus) infection of AGMs despite similarly high viral replication. PMN death was a Bax and Bak-independent mitochondrial insult, which is prevented by inhibiting calpain activation but not caspases. We found that BOB/GPR15, a SIV coreceptor, is expressed on the PMN surface of RMs at a much higher levels than AGMs and its ligation induced PMN death, suggesting that SIV particle binding to the cell surface is sufficient to induce PMN death. Taken together, our results suggest that species-specific differences in BOB/GPR15 receptor expression on PMN can lead to increased acute phase PMN death. This may account for the decline in PMN numbers that occurs during primary SIV infection in pathogenic SIV infection and may have important implications for subsequent viral replication and disease progression.
Elbim
Carole
C
Faculté de Médecine, Service d'Immunologie et d'Hématologie,Assistance Publique-Hôpitaux de Paris, Centre Hospitalier Universitaire Xavier Bichat, Université Paris 7-Denis Diderot, Paris, France.
Monceaux
Valerie
V
Mueller
Yvonne M
YM
Lewis
Mark G
MG
François
Stephanie
S
Diop
Ousmane
O
Akarid
Khadija
K
Hurtrel
Bruno
B
Gougerot-Pocidalo
Marie-Anne
MA
Lévy
Yves
Y
Katsikis
Peter D
PD
Estaquier
Jerome
J
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D008137:Longitudinal Studies; D008231:Lymphopenia / Q000276:immunology / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D008992:Monkey Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity*; D013045:Species Specificity; D013997:Time Factors