Host nutritional status affects alphavirus virulence, transmission, and evolution.

James Weger-Lucarelli,Tanya Leroith,Marco Vignuzzi,Jérémy Boussier,Daniela Megrian,Sheryl Coutermarsh-Ott,Hervé Blanc,Thomas Vallet,Lucia Carrau,Veronica Rezelj,Laura I Levi,Richard J Kuhn

doi:10.1371/journal.ppat.1008089

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.

Highlights

Arthritogenic alphaviruses are globally distributed and have been responsible for several recent large outbreaks
While the rise in global travel, the spread of mosquito vectors, and climate change are likely involved in the expansion of these viruses, it is conceivable that changes in human health have facilitated spread
Mayaro virus (MAYV) strain TRVL 4675 and River virus (RRV) strain T48 were obtained from the Centers for Disease Control and Prevention (CDC, Fort Collins, Colorado, USA) and infectious clones were constructed under an SP6 promoter in the same plasmid backbone of the chikungunya virus (CHIKV) clone described above

Summary

Introduction

Arthritogenic alphaviruses are globally distributed and have been responsible for several recent large outbreaks. Chikungunya virus (CHIKV) re-emerged in 2004 to cause a massive outbreak in the Indian Ocean region [1], which subsequently spread to the Americas in 2013, resulting in millions of cases [2]. Mayaro virus (MAYV), traditionally confined to sylvatic transmission in South America, was recently isolated in Haiti for the first time, serving as a warning that urban transmission can occur [5]. Arthritogenic alphaviruses produce a disease that is characterized by fever, myalgia, and polyarthralgia, which can last for months or even years [6,7]. Roughly 10% of the adult population worldwide is considered underweight [12]. Over- and underweight, along with nutrient deficiencies, can be classified together as malnutrition and commonly occur in the same country or even within the same family [13]

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