Host nutritional status affects alphavirus virulence, transmission, and evolution

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.

Nutritional status impacts dengue virus infection in mice

“…The relevance of the increased spleen pathology observed here is unclear since mice produced no overt symptoms following infection. We previously found increased disease severity in PEM mice infected with chikungunya virus or Mayaro virus [66], suggesting that this observation may be true for many viral infections. The results of our studies are tempered by the existence of many forms of undernutrition, including PEM, but also micronutrient deficiencies, underweight, wasting, and stunting [67].…”

They are what you eat: Shaping of viral populations through nutrition and consequences for virulence

“…We observed a significant increase in viral diversity and subsequent virulence after a single round of infection, with the phenotype persisting in obese-derived viral populations across 10 passages [41]. Interestingly, arbovirus-infected obese or protein-deficient mice showed higher morbidity but lower viral diversity, and both malnourished models transmitted virus less efficiently, highlighting that the effects of nutrition may vary based on the natural life cycles of viral families [42]. It is yet to be determined how malnourishment may impact transmission of a respiratory, as compared with a vector-borne, virus.…”

Coronavirus Disease 2019 (COVID-19) and Nutritional Status: The Missing Link?

“…Obese individuals present additionally, a delayed capacity of IFN production, which allows higher viral RNA replication, consequently increasing the opportunity of the emergence of novel, more virulent viral strains ( 38 , 49 ). Obesity is also associated with epithelial dysfunction and increased permeability, which could permit rapid virus shedding from the tissue and, consequently, faster spreading ( 50 ). Based on these data, it is possible to infer that obesity could have a potential role in the transmission of SARS-CoV-2 ( 51 ).…”