The U.S. Four Corners region, where Arizona, New Mexico, Utah, and Colorado converge, supports diverse ecosystems, high rodent biodiversity, and increasing human–wildlife contact, making it a critical area for monitoring emerging infectious diseases. Over the past century, New Mexico has undergone a tenfold population increase, accompanied by expanding urban and agricultural development. These shifts, coupled with climate-driven changes in vector and reservoir distributions, are thought to underlie the state’s persistently high incidence of hantavirus pulmonary syndrome since national surveillance began in 1993. Recently, Sin Nombre virus (SNV) was detected in several rodent species, including six not previously recognized as hosts. Together, these trends emphasize the need for proactive surveillance strategies to anticipate and prevent zoonotic spillover.
To address this need, we implemented a two-pronged approach integrating serological profiling with genomic detection. We analyzed serum and tissue samples from small mammals collected across New Mexico to assess exposure to a panel of viral and bacterial pathogens and to identify high-priority candidates for next-generation sequencing (NGS). Using a high-throughput MAGPIX multiplex immunoassay, we screened more than 700 serum samples representing over 22 species, revealing widespread exposure to pathogens endemic and non-endemic to this region of the United States. SNV-seropositive cases were further investigated through quantitative PCR to confirm active infection and narrow down top candidates for sequencing. NGS revealed mutations and diversity of circulating variants that may affect epitope structure and influence the performance of existing medical countermeasures.
By coupling broad immunological screening with targeted viral genomics, this work provides a scalable surveillance model to study pathogen exposure and transmission dynamics. Additionally, it can help inform early warning systems and strengthen national preparedness for future zoonotic threats.
