[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Host nutritional status affects alphavirus virulence, transmission, and evolution
James Weger-Lucarelli , Lucia Carrau, Laura I. Levi, Veronica Rezelj, Thomas Vallet, Hervé Blanc, Jérémy Boussier, Daniela Megrian, Sheryl Coutermarsh-Ott, Tanya LeRoith, Marco Vignuzzi
Published: November 11, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1008089 / This is an uncorrected proof.
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.
Over- and undernutrition, collectively known as malnutrition, affect over 2.5 billion people worldwide. Associations between malnutrition and mosquito-borne virus infection and resulting disease have been identified in epidemiological studies but have not been explored in controlled studies. Here, we infect obese or undernourished mice with different arthritis inducing viruses in the genus Alphavirus and measure disease symptoms, viral replication, transmission, and evolution. We found that markers of disease, namely weight loss and footpad swelling, were increased in obese mice. We also found that replication differences between mice fed different diets were minimal except late in infection for obese mice when levels of virus dropped significantly. When mosquitoes were allowed to feed on mice fed different diets, we observed reduced infection and transmission rates, depending on the diet. Finally, we found reduced genetic diversity and replicative fitness of virus isolated from obese mice. This study provides insights into the influence of nutrition on alphavirus pathogenesis and evolution.
Citation: Weger-Lucarelli J, Carrau L, Levi LI, Rezelj V, Vallet T, Blanc H, et al. (2019) Host nutritional status affects alphavirus virulence, transmission, and evolution. PLoS Pathog 15(11): e1008089. https://doi.org/10.1371/journal.ppat.1008089
Editor: Richard J. Kuhn, Purdue University, UNITED STATES
Received: June 23, 2019; Accepted: September 17, 2019; Published: November 11, 2019
Copyright: © 2019 Weger-Lucarelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All next-generation sequencing files are uploaded to the small read archive (SRA) under accession number PRJNA573904.
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
Competing interests: The authors have declared that no competing interests exist.
Keywords: Arbovirus; Alphavirus; Mosquitoes; Animal models.