Γ-herpesvirus latency attenuates Mycobacterium tuberculosis infection in mice. (May 2019)

• Record Type: Journal Article
• Authors: Miller, Halli E.; Johnson, Kaitlin E.; Tarakanova, Vera L.; Robinson, Richard T.
• Is Part Of: Tuberculosis. Volume 116(2019)
• Page Start: 56
• Page End: 60
• Publication Date: 2019-05
• Subjects: 616.995
• DOI: 10.1016/j.tube.2019.04.022
• Languages: English
• ISSNs: 1472-9792

Abstract

Abstract: Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), a bacterial pathogen which is transmitted via aerosol and establishes a chronic lung infection. In naïve hosts, Mtb grows for several weeks without being restricted by IFNγ-producing T cells, which eventually accumulate and limit Mtb dissemination. In this study, we used a mouse model of Mtb/γ-herpesvirus (γHV) coinfection to test the hypothesis that latent γHV infection alters host resistance to Mtb. γHVs are DNA viruses which elicit a polyclonal T cell response and attenuate some acute bacterial pathogens in mice; whether γHVs modulate infection with Mtb is unknown. Here, mice harboring latent mouse gammaherpesvirus 68 (MHV68)—a γHV genetically and biologically related to human Epstein Barr virus (EBV)—were infected via aerosol with a low dose of virulent Mtb. Mtb burdens and IFNγ + T cell frequencies in mice with latent MHV68 (MHV68 POS mice) were subsequently measured and compared to control mice that did not harbor latent MHV68 (MHV68 NEG mice). Relative to MHV68 NEG controls, MHV68 POS mice more effectively limited Mtb growth and dissemination, and had higher frequencies of CD4+IFNγ+ cells in lung-draining lymph nodes. Collectively, our results support a model wherein latent γHV confers moderate protection against subsequent Mtb infection.