Effect of Hantavirus Infection on the Rodent Lung Microbiome: Specific Regulatory Roles of Host Species and Virus Types

The lung-targeting characteristic of <i>Hantavirus</i> infection and the unclear mechanism underlying its interaction with the lung microbiome hampers the development of effective prevention and control strategies. In this study, lung tissues from <i>Apodemus agrarius</i> and <i>Rattus norvegicus</i> were collected at <i>Hantavirus</i> surveillance sites in Hunan Province. Metagenomic sequencing was subsequently applied to compare microbiome diversity, community structure, and function between infected and uninfected groups. Then the linear discriminant analysis effect size (LEfSe) was employed to identify key biomarkers. The results indicated that after infection with <i>Hantaan virus</i> (HTNV), <i>Apodemus agrarius</i> exhibited significantly increased evenness but markedly decreased richness of lung microbial communities, as reflected by consistent reductions in the number of observed species, Abundance-based Coverage Estimator (ACE) index, and Chao1 index. In contrast, <i>Rattus norvegicus</i> infected with <i>Seoul virus</i> (SEOV) showed no significant difference in microbial richness compared with uninfected controls, and even a slight increase was observed. These findings suggest that host species and virus type may play an important role in shaping microbial community responses. Furthermore, β-diversity analysis showed that the community structure was clearly separated by the host rodent species, as well as by their virus infection status. LEfSe analysis identified taxa with discriminatory power associated with infection status. <i>Streptococcus agalactiae</i> and <i>Streptococcus</i> were associated with SEOV-infected <i>Rattus norvegicus</i>, while <i>Chlamydia</i> and <i>Chlamydia abortus</i> were relatively enriched in uninfected <i>Apodemus agrarius</i>. This exploratory study reveals preliminary association between specific host-<i>Hantavirus</i> pairings (HTNV-<i>Apodemus agrarius</i> and SEOV-<i>Rattus norvegicus</i>) and the rodent lung microbiome, offering potential insights for future research into viral pathogenesis.