Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques.
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.
Dhillon
Navneet Kaur
NK
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Pinson
David
D
Dhillon
Sukhbir
S
Tawfik
Ossama
O
Danley
Marsha
M
Davis
Marilyn
M
Nemon
Olga
O
Mayo
Matthew
M
Kumar
Anil
A
Tsai
Yi-Jou
YJ
Kumar
Amit
A
Buch
Shilpa
S
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D007150:Immunohistochemistry; D016180:Lentivirus Infections / Q000473:pathology*; D008168:Lung / Q000821:virology*; D008251:Macaca; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects*
D001761:Bleomycin