Role of virus replication in a murine model of AIDS-associated interstitial pneumonitis.
One of the major complications of HIV infection is the development of interstitial pneumonitis (IP). IP is characterized by lymphocytic infiltration of the lung and may lead to respiratory failure in some cases. The etiology of IP is unknown although it is likely the result of an antiviral or autoimmune response occurring in the lung. To determine the role of viral replication in the development of IP, AZT was evaluated for the ability to inhibit development of lung inflammation in a murine model of retrovirus-associated IP. Mice were infected with LP-BM5 retrovirus, which induces murine AIDS. Infected mice develop IP by 4 weeks postinfection characterized by infiltration of the lung with activated T cells, B cells, and macrophages. Virus could be detected in the lungs of these mice by 2 weeks postinfection and persisted throughout the course of disease. To determine if reduction in viral load affected the disease process, infected mice were treated with AZT for varying periods postinfection and analyzed for the development of IP. Treatment with AZT resulted in a treatment time-dependent reduction of viral RNA in the lungs of infected mice compared to untreated infected mice. The reduction of viral burden in the lungs correlated with a reduction in the severity of IP and decreased production of the proinflammatory cytokines interleukin (IL)-1 beta and interferon (IFN)-gamma. These results suggest that continuous viral replication in the lung contributes to the pathogenesis of IP.
Fitzpatrick
E A
EA
Department of Microbiology and Immunology, University of Kentucky College of Medicine, Lexington, KY 40536-0084, USA.
Avdiushko
M
M
Kaplan
A M
AM
Cohen
D A
DA
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000821:virology; D017563:Lung Diseases, Interstitial / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D016207:Cytokines; D015215:Zidovudine