Deadly interactions: Synergistic manipulations of concurrent pathogen infections potentially enabling future pandemics

Abstract

Certain monoinfections of influenza viruses and novel coronaviruses, including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are significant threats to human health. Concurrent infections by influenza viruses and coronaviruses increases their threat. Influenza viruses have eight manipulations capable of assisting SARS-CoV-2 and other coronaviruses, and several of these manipulations, which are not specific to viruses, can also directly or indirectly boost dangerous secondary bacterial pneumonias. The influenza virus manipulations include: inhibiting transcription factors and cytokine expression; impairing defensive protein expression; increasing RNA viral replication; inhibiting defenses by manipulating cellular sensors and signaling pathways; inhibiting defenses by secreting exosomes; stimulating cholesterol production to increase synthesized virion infectivities; increasing cellular autophagy to assist viral replication; and stimulating glucocorticoid synthesis to suppress innate and adaptive immune defenses by inhibiting cytokine, chemokine, and adhesion molecule production. Teaser: Rapidly spreading multidrug-resistant respiratory bacteria, combined with the far-reaching cellular defense manipulations of influenza virus benefiting evolving SARS-CoV-2 or other coronaviruses and/or respiratory bacteria, can enable severe future pandemics or co-pandemics.