Gammaherpesvirus Infection Stimulates Lung Tumor-Promoting Inflammation.

Area of Science:

• Oncology
• Virology
• Immunology

Background:

• Environmental exposures and gamma herpesvirus (γHV) infections are linked to Type 17 inflammation.
• γHV infections are increasingly recognized for their potential role in tumorigenesis.

Purpose of the Study:

• To investigate the effect of γHV infection on lung tumor promotion in a K-Ras mutant mouse model.
• To explore the associated inflammatory and immune responses.

Main Methods:

• K-Ras mutant mice (K-Ras^LA1) and wild-type littermates were infected with MHV68 via oropharyngeal aspiration.
• Lung tumors, cytokine expression (IL-6, CXCL1, CSF3), immune cell populations (Ly6G^dim/Ly6C^hi), and mRNA methylation (m⁶A) were assessed post-infection.

Main Results:

• MHV68 infection led to a >2-fold increase in lung tumors in K-Ras^LA1 mice compared to uninfected controls.
• Type 17 cytokines (IL-6, CXCL1, CSF3) peaked at 7 days post-infection, correlating with tumor promotion.
• Infected K-Ras^LA1 mice showed increased Ly6G^dim/Ly6C^hi immune cells and elevated CSF3/CXCL1 protein levels, with m⁶A modification potentially linked to inflammatory infiltrates.

Conclusions:

• γHV infection promotes lung tumorigenesis in K-Ras mutant mice.
• The infection induces a Type 17 inflammatory response and selective accumulation of specific immune cells in the lungs.
• m⁶A modification of mRNAs in immune cells may be associated with these inflammatory infiltrates, implicating a novel mechanism in virus-driven lung cancer.