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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/L1233    most recent 00293.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Dhillon, N. K. Articles by Buch, S. Search for Related Content PubMed PubMed Citation Articles by Dhillon, N. K. Articles by Buch, S.

Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques

¹Department of Molecular and Integrative Physiology, ²Department of Pathology and Laboratory Medicine, ³Department of Microbiology, Immunology, and Molecular Genetics, ⁴Center for Biostatistics and Advanced Informatics, and ⁶Cardiovascular Disease, University of Kansas Medical Center, and ⁵University of Missouri Kansas City, Kansas City, Kansas

Submitted 4 August 2006 ; accepted in final form 6 January 2007

Pneumonia is a major complication of human immunodeficiency virus (HIV) pathogenesis but it develops only after prolonged infection. We used the macaque model to explore a hypothesis that the disease is a two-stage process, the first stage being establishment of the viral infection in the lung and the second being amplification of virus replication by host factors induced by chemical agents or opportunistic pathogens in the lung. Bleomycin, a chemical known to induce diffuse alveolar damage and pulmonary fibrosis with accumulation of macrophages and a rich T helper type 2 (Th2) cytokine environment, was inoculated intratracheally into five of eight SHIV 89.6P-infected macaques and into one uninfected macaque. Three additional simian HIV (SHIV)-infected macaques without bleomycin treatment served as untreated virus controls. Although none of the animals became clinically ill, bleomycin induced classical host responses in the lungs of all the treated, virus-infected macaques. There was enhanced production of the chemokine, monocyte chemotactic protein-1 (MCP-1), that had previously been shown to cause enhanced replication of the virus. Four of the five treated animals developed more productive SHIV infection in the lungs compared with the infected untreated animals. Enhanced virus replication was found primarily in infiltrating macrophages. Enhanced replication of the virus in the lungs was associated with host factors induced by the drug and supported the hypothesis for a two-stage process of pulmonary pathogenesis.

simian-human immunodeficiency virus