title: Secretion of beta-chemokines by bronchoalveolar lavage cells during primary infection of macaques inoculated with attenuated nef-deleted or pathogenic simian immunodeficiency virus strain mac251.
abstract: Primary infection of macaques with simian immunodeficiency virus (SIV) as a model of human immunodeficiency virus (HIV) infection represents a unique opportunity to investigate early lentivirus-host interactions. In order to gain insight into immunopathogenic events taking place in the lung during lentiviral infection, we analysed lymphocyte expansion in the lung and chemokine secretion by mononuclear cells obtained by bronchoalveolar lavage (BALMCs) during primary infection by a pathogenic and a non-pathogenic SIV. Two groups of cynomolgus macaques were inoculated intravenously with a fully pathogenic isolate of SIVmac251 or with an attenuated, nef-deleted, molecular clone of SIVmac251. Spontaneous MIP-1alpha, MIP-1beta and RANTES production was assessed by ELISA in supernatants of short-term cultured BALMCs. Kinetics of haematological, virological and immunological parameters were investigated simultaneously. All 11 inoculated animals became infected. Monkeys inoculated with the nef-deleted SIV clone exhibited a significantly reduced plasma virus load and a less pronounced accumulation of lymphocytes in the lung compared to monkeys infected with the pathogenic SIVmac251 isolate. Compared to pre-infection levels, we observed an increase in the levels of RANTES, MIP1-alpha and MIP1-beta production in the two groups of monkeys, by the time of peak viraemia. Strikingly, a greater enhancement of RANTES and MIP-1alpha production was detected in monkeys infected with the attenuated virus. Given the potential influence of beta-chemokines on the immune response and virus replication, such results suggest that RANTES, MIP1-alpha and MIP1-beta could contribute to the singular features of the immune response elicited during infection of macaques with an attenuated SIV.
authors: P
authors: P
authors: Caufour
authors: R
authors: R
authors: Le Grand
authors: A
authors: A
authors: Ch Ret
authors: O
authors: O
authors: Neildez
authors: F
authors: F
authors: Th Odoro
authors: B
authors: B
authors: Boson
authors: B
authors: B
authors: Vaslin
authors: D
authors: D
authors: Dormont
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology* / Q000821:virology; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D019742:Chemokines, CC / Q000096:biosynthesis*; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D017353:Gene Deletion; D015754:Genes, nef / Q000235:genetics*; D016679:Genome, Viral; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000821:virology; D016131:Lymphocyte Subsets / Q000276:immunology; D008252:Macaca fascicularis; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013997:Time Factors; D019562:Viral Load
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D004279:DNA, Viral; D019402:Macrophage Inflammatory Proteins; D012367:RNA, Viral