title: Simian human immunodeficiency virus-associated pneumonia correlates with increased expression of MCP-1, CXCL10, and viral RNA in the lungs of rhesus macaques.
abstract: Pulmonary disorders are the most frequent cause of death in HIV-1-infected individuals with AIDS and remain important even in the current era of potent antiretroviral therapy. Macaques infected with Simian/Human Immunodeficiency Virus (SHIV) develop pulmonary disease and concurrent opportunistic infections similar to those observed in HIV-infected individuals, thereby providing an excellent working model to elucidate the pathogenesis of the human lung disease. Since chemokines play a crucial role in the recruitment of inflammatory cells to tissues, we investigated the relationship between respiratory disease and the levels of chemokines, monocyte chemotactic protein-1 (MCP-1) and CXCL10, in the lungs of SHIV-infected rhesus macaques. We found that lung pathology in infected macaques was closely associated with overexpression of MCP-1 and CXCL10. In addition, these chemokines could, in part, be responsible for the recruitment of inflammatory cells infiltrating into the diseased lungs as demonstrated by chemotactic assays. Lung pathology and increased levels of MCP-1 and CXCL10 correlated with high viral loads in the lung parenchyma. Using confocal microscopy, we identified SHIV-infected macrophages as the major producers of MCP-1 and CXCL10 in the diseased lungs. These data suggest that chemokine overexpression plays an important role in the pathogenesis of SHIV-associated pulmonary disease in macaques.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, Marion Merrell Dow Laboratory of Viral Pathogenesis, 5000 Wahl Hall East, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Sui
authors.forename: Shanping
authors.initials: S
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Pinson
authors.forename: Istvan
authors.initials: I
authors.lastname: Adany
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Li
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Opendra
authors.initials: O
authors.lastname: Narayan
authors.forename: Shilpa
authors.initials: S
authors.lastname: Buch
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015497:HIV-1 / Q000378:metabolism*; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008251:Macaca; D008253:Macaca mulatta / Q000821:virology*; D008264:Macrophages / Q000378:metabolism; D008856:Microscopy, Fluorescence; D011014:Pneumonia / Q000821:virology*; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology
chemical_list: C515334:CCR2 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D012333:RNA, Messenger; D012367:RNA, Viral; D054390:Receptors, CCR2; D019707:Receptors, Chemokine