Viral gene expression in HIV transgenic mice is activated by Mycobacterium tuberculosis and suppressed after antimycobacterial chemotherapy.
We used human immunodeficiency virus (HIV) transgenic (Tg) mice incorporating the entire viral genome to study the effect of Mycobacterium tuberculosis infection on the induction of integrated HIV gene expression. When aerogenically infected with M. tuberculosis, these mice displayed a progressive increase in pulmonary gag and env mRNA levels and of p24 antigen production by cultured splenocytes. In situ hybridization of lungs revealed increased viral transcription associated with areas of inflammation and acid-fast bacilli. By neutralizing tumor necrosis factor (TNF) in vivo after M. tuberculosis exposure, we found that, although initially TNF independent, the increased HIV expression triggered by M. tuberculosis was highly dependent on this cytokine by 4 weeks after infection. Furthermore, treatment with antimycobacterial drugs markedly reduced HIV transgene expression. These studies establish an animal model for investigating the influence of M. tuberculosis on latent HIV expression and for testing therapeutic regimens for reducing the disease burden in patients with acquired immunodeficiency syndrome-associated tuberculosis.
Scanga
Charles A
CA
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA.
Bafica
Andre
A
Sher
Alan
A
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000472:pathogenicity*; D013154:Spleen / Q000166:cytology / Q000821:virology; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
D000995:Antitubercular Agents; D015686:Gene Products, env; D015683:Gene Products, gag; D016655:HIV Core Protein p24