Exogenous Chemical Exposure Increased Transcription Levels of the Host Virus Receptor Involving Coronavirus Infection

Virus receptors are highly involved
in mediating the entrance of
infectious viruses into host cells. Here, we found that typical chemical
exposure caused the upregulation of virus receptor mRNA levels. Chemicals
with the same structural characteristics can affect the transcription
of angiotensin-converting enzyme 2 (ACE2), a dominant
receptor of SARS-CoV-2. Some chemicals can also regulate the transcription
of ACE2 by similar regulatory mechanisms, such as
multilayer biological responses and the crucial role of TATA-box binding
protein associated factor 6. The abovementioned finding suggested
that chemical mixtures may have a joint effect on the ACE2 mRNA level in the real scenario, where humans are exposed to numerous
chemicals simultaneously in daily life. Chemically regulated virus
receptor transcription was in a tissue-dependent manner, with the
highest sensitivity in pulmonary epithelial cells. Therefore, in addition
to genetic factors, exogenous chemical exposure can be an emerging
nongenetic factor that stimulates the transcription of virus receptor
abundance and may elevate the protein expression. These alterations
could ultimately give rise to the susceptibility to virus infection
and disease severity. This finding highlights new requirements for
sufficient epidemiological data about exposomes on pathogen receptors
in the host.