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Low temperature increases adenovirus replication via intracellular alkalization.

Wenwu Sun1, Zhuang Ma1, Jianping Cao1

  • 1Department of Respiratory Medicine, General Hospital of Northern Theatre Command, Shenyang, China.

Frontiers in Cellular and Infection Microbiology
|October 24, 2025
PubMed
Summary

Lower temperatures enhance adenovirus replication in lung cells by increasing intracellular pH and promoting glycolysis. Inhibiting glycolysis or acidifying the external environment reduces this effect, revealing a link between temperature, cell metabolism, and viral infection.

Keywords:
adenovirus replicationglycolysisintracellular alkalizationlow temperaturethe common cold

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Area of Science:

  • * Virology
  • * Cell Biology
  • * Environmental Health

Background:

  • * Respiratory viral infections are more common in colder months.
  • * The impact of low temperatures on pulmonary epithelial cells and viral replication is not fully understood.
  • * Adenovirus is a common cause of respiratory illness.

Purpose of the Study:

  • * To investigate the effect of low temperature on adenovirus replication in A549 pulmonary epithelial cells.
  • * To determine the role of intracellular pH (pHi) and glycolysis in temperature-dependent viral replication.

Main Methods:

  • * Cultured A549 cells were exposed to different temperatures (33°C and 37°C).
  • * Intracellular pH (pHi) was measured.
  • * Adenovirus replication was quantified.
  • * Glycolysis was inhibited using 2-deoxy-D-glucose (2-DG) or PFK158.
  • * Oligomycin was used to stimulate glycolytic flux.
  • * Extracellular medium pH was adjusted.

Main Results:

  • * A cooler temperature (33°C) increased both intracellular pH (alkalization) and adenovirus replication.
  • * Inhibition of glycolysis attenuated the enhanced viral replication at 33°C.
  • * Stimulation of glycolysis with oligomycin increased viral replication at 37°C.
  • * Low-temperature-induced viral replication and alkalization were inhibited by extracellular acidification.

Conclusions:

  • * Low environmental temperatures enhance adenovirus replication in pulmonary epithelial cells.
  • * This enhancement is mediated by temperature-induced intracellular alkalization and increased glycolysis.
  • * Targeting cellular pH and glycolysis may offer strategies to control temperature-dependent viral infections.