Host nutritional status affects alphavirus virulence, transmission, and evolution

PLoS Pathog. 2019 Nov 11;15(11):e1008089. doi: 10.1371/journal.ppat.1008089. eCollection 2019 Nov.

Abstract

Malnourishment, specifically overweight/obesity and undernourishment, affects more than 2.5 billion people worldwide, with the number affected ever-increasing. Concurrently, emerging viral diseases, particularly those that are mosquito-borne, have spread dramatically in the past several decades, culminating in outbreaks of several viruses worldwide. Both forms of malnourishment are known to lead to an aberrant immune response, which can worsen disease outcomes and reduce vaccination efficacy for viral pathogens such as influenza and measles. Given the increasing rates of malnutrition and spread of arthropod-borne viruses (arboviruses), there is an urgent need to understand the role of host nutrition on the infection, virulence, and transmission of these viruses. To address this gap in knowledge, we infected lean, obese, and undernourished mice with arthritogenic arboviruses from the genus Alphavirus and assessed morbidity, virus replication, transmission, and evolution. Obesity and undernourishment did not consistently influence virus replication in the blood of infected animals except for reductions in virus in obese mice late in infection. However, morbidity was increased in obese mice under all conditions. Using Mayaro virus (MAYV) as a model arthritogenic alphavirus, we determined that both obese and undernourished mice transmit virus less efficiently to mosquitoes than control (lean) mice. In addition, viral genetic diversity and replicative fitness were reduced in virus isolated from obese compared to lean controls. Taken together, nutrition appears to alter the course of alphavirus infection and should be considered as a critical environmental factor during outbreaks.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aedes / virology*
  • Alphavirus / pathogenicity*
  • Alphavirus Infections / etiology*
  • Alphavirus Infections / pathology
  • Alphavirus Infections / transmission*
  • Animals
  • Biological Evolution*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Mosquito Vectors / virology
  • Nutritional Status*
  • Obesity / pathology
  • Obesity / virology*
  • Virulence
  • Virus Replication

Grants and funding

This work was partially funded by the DARPA program PREventing EMerging Pathogenic Threats (PREEMPT) awarded to MV and JWL. Partial funding was also provided by a faculty start-up package at Virginia Tech awarded to JWL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript