Effects of high temperature on pandemic and seasonal human influenza viral replication and infection-induced damage in primary human tracheal epithelial cell cultures

Abstract

High temperature reduces influenza viral replication; however, the treatment of fevers is thought to be necessary to improve patients' conditions. We examined the effects of high temperature on viral replication and infection-induced damage to human tracheal epithelial cells. Cell viability and dome formation were reduced, the number of detached cells was increased and lactate dehydrogenase (LDH) levels tended to be increased from 72 h to 120 h in uninfected cells cultured at 40 °C. Long-term (72 h and/or 120 h) exposure to high temperatures (39 °C and/or 40 °C) decreased RNA levels and/or viral titers of eight influenza virus strains. Cell viability and dome formation were reduced, and the number of detached cells and LDH levels were increased to a similar extent after infection with the A/H1N1 pdm 2009 virus at 37 °C and 40 °C. High temperature increased the endosomal pH, where the viral RNA enters the cytoplasm, in uninfected cells. High temperature reduced the production of IL-6, which mediate viral replication processes, and IL-1β and IL-8 in uninfected and infected cells. Based on these findings, high temperature may cause similar levels of airway cell damage after infection to cells exposed normal temperatures, although high temperature reduces viral replication by affecting the function of acidic endosomes and inhibiting IL-6-mediated processes.

Polymers in the Medical Antiviral Front-Line

“…Similar conclusions were reported by Molla et al while studying the effect of temperature on Poliovirus formation and RNA synthesis [154]. Yamaya et al, however, showed that, above 37 °C, the Influenza viruses' replication decrease [155], while Reed showed that for Panonychus-citri's nonoccluded virus, the biocidal temperature (above which the virus population is damaged) is 46 °C [156]. Chan, et al showed that for SARS-CoV, the biocidal temperature is <38 °C [157] and Harrison showed that Rothamsted Tobacco Necrosis virus biocidal temperature is even lower than Influenza's [158].…”

Kakkonto, shosaikoto, Platycodon grandiflorum root, and gypsum (a Japanese original combination drug known as saikatsugekito): Pharmacological review of its activity against viral infections and respiratory inflammatory conditions and a discussion of its applications to COVID‐19

“…According to the present review, KKT treatment increased body temperature, whereas the combination of gypsum and Ephedra herb decreased body temperature. High temperature reduced the replication of influenza A virus by affecting the function of acidic endosomes and inhibiting IL‐6‐mediated processes [70], which is mainly important during the acute phase of infection. On the other hand, a consistently high temperature can cause general malaise and fatigue.…”

Effect of a fever in viral infections — the ‘Goldilocks’ phenomenon?

“…The influenza virus is internalised via receptor-mediated endocytosis, which requires an acidic environment for the endosome to trigger viral and endosomal membrane fusion[ 34 , 35 ]. High temperatures appear to increase endosomal pH, adversely affecting influenza virus entry and intracellular transportation[ 36 ].…”

“…While the viral messenger RNA transcription may be maintained at higher temperatures, genome replication is markedly reduced, due to reduced association of the polymerase with positive-sense RNA templates[ 41 ]. A raised temperature also appears to cause a reduction in the cytokine interleukin (IL)-6 levels after human cell infection with influenza virus[ 36 ]; IL-6 is required for a number of cytokine-mediated processes involved in viral replication[ 42 ].…”