Emergence and molecular evolution of tacaribe virus as a human pathogen

The National Institute of Allergy and Infectious Diseases awarded the University of Texas Medical Branch at Galveston $243,704 on September 2, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate the molecular evolution and human pathogenic potential of Tacaribe virus.

The funded research examines in vitro host range of Tacaribe virus and its prevalence in Peru, specifically determining whether viral mutations enable the virus to use the human transferrin receptor 1 for cell entry—a mechanism implicated in human disease potential of related mammarenaviruses. The project pursues two aims: establishing prevalence of Tacaribe virus infection among patients with acute undifferentiated febrile illness in the Peruvian Amazon between 2020 and 2025, and investigating viral host range, replication characteristics, and transferrin receptor 1 usage of historical and recent human isolates. The work leverages existing collaboration with investigators at the United States Naval Medical Research South laboratory. Recent genomic analyses of Peruvian human isolates revealed seven amino acid substitutions compared to the prototype Trinidad and Tobago strain, including three critical changes in the viral glycoprotein.

Work is performed in Galveston, Texas. The period of performance runs from the award date through August 31, 2028. This is a Project Grant, an assistance type under the NIAID program supporting biomedical research and research training in infectious diseases.

Abstract

Tacaribe virus (tcrv), a mammarenavirus, was initially identified in bats in trinidad and tobago in 1956. More recently, its presence in the U.S. Was confirmed in 2012 with its isolation from amblyomma americanum ticks in a florida state park. Recent surveillance studies for febrile illnesses in peru led to a significant finding: tcrv was isolated from the serum of two patients experiencing acute undifferentiated febrile illness (aufi). While one patient recovered from the infection, the outcome for the second patient remains uncertain. Comprehensive genome sequencing analyses of these peruvian human tcrv isolates revealed seven amino acid substitutions compared to the prototype tcrv isolate from trinidad and tobago, with three of these critical changes occurring in the glycoprotein (GP). This proposal seeks to examine experimentally the in vitro host range of tcrv and its potentially hidden prevalence in peru. Specifically, we will determine if the virus has adapted to use the human transferrin receptor 1 (HTFR1) for cell entry, a mechanism implicated in the human disease potential of other clade b mammarenaviruses. Furthermore, utilizing our existing collaboration with investigators at the united states naval medical research south (namru south) laboratory, we will assess the prevalence of tcrv in febrile patients from peru. We hypothesize that the specific mutations in tcrv's GP have enabled the virus to use HTFR1 as a receptor, thereby expanding its host range to humans, leading to an increase in aufi cases in peru over the past years. To test this, we will pursue two aims: 1) establish the prevalence of tcrv infection among patients diagnosed with aufi in the peruvian amazon, between 2020-2025, and 2) investigate the viral host range, replication characteristics, and HTFR1 usage of historical and recent human tcrv isolates. This project is expected to generate critical insights into tcrv's emergence. Given the presence of tcrv in the U.S., understanding the factors driving its emergence is essential for developing strategies to prevent future tcrv infections and mitigate its public health impact.