Temperature dependent viral tropism: understanding viral seasonality and pathogenicity as applied to the avoidance and treatment of endemic viral respiratory illnesses

Abstract

Summary This review seeks to explain three features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness and the rapid response of outbreaks to weather, specifically temperature; (2) the common viruses causing respiratory illness worldwide, including year‐round disease in the Tropics; (3) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called temperature dependent viral tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can spread more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ‐specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature . This can confine them to the upper respiratory tract and allow them to avoid infecting the lungs, heart, gut etc. Biochemical and tissue‐culture studies show that ‘wild’ respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the occurrence of respiratory illness in the Tropics year‐round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. TDVT has important practical implications for preventing and treating respiratory illness including Covid‐19. It is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.

Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths

“…Note that influenza activity was approximated by ILI which has been proposed to be more a measure of pathogen interference that influenza activity per se. It has been suggested that respiratory viruses adapt their thermal sensitivity to local conditions, hence influenza outbreaks in the tropics [ 240 ]—implying a range of influenza variants with latitude.…”

Mutation Effects on Structure and Dynamics: Adaptive Evolution of the SARS-CoV-2 Main Protease

“…19,20 Differences in host body temperatures impose different thermodynamic and kinetic constraints on the structure and activity of viral proteins within cells, which is a known factor limiting inter-species virus transmission 21,22 as well as tissue tropism within a single host. 23,24 As shown in studies of extremophilic organisms, the stability and catalytic efficiency of enzymes are dependent on their thermal environments. 25,26 Proteins in organisms that regularly experience high temperatures require stronger and more extensive interactions among residues, such as disulfide bonds and salt bridges to maintain stability, 27−29 proteins in low-temperature regimes require greater internal flexibility to facilitate catalysis.…”

The natural thermal sensitivity of SARS-CoV-2

“…We recently published a review of the factors underlying the winter seasonality and pathogenicity of respiratory viruses [1] . We showed that many respiratory viruses possess natural thermal sensitivity, meaning they replicate faster at temperatures below their hosts’ normal body temperature, confining them to the upper airways.…”

“…Our analysis and hypothesis have important practical implications for clinical practice. For example, standing still outside and wearing insufficiently warm winter clothing are correlated with increased risk of death from respiratory illness [1] . This suggests that steps taken by individuals to avoid chilling may be protective.…”

“…Moreover, personal chilling after contracting a respiratory illness may increase disease severity. We suggest randomized controlled trials of advice to healthy individuals to avoid chilling in order to reduce the frequency of respiratory illnesses, and trials of interventions in clinical settings to prevent chilling of sick patients with respiratory illnesses in order to reduce disease severity [ 1 , 10 ].…”