In a published case-control study (GSE152075) from SARS-CoV-2 positive (n=403) and negative patients (n=50), we analyzed the response to infection assessing gene expression of host cell receptors and antiviral proteins. The expression analysis associated with reported risk factors for COVID-19 was also assessed. SARS-CoV-2 cases had higher
ACE2
, but lower
TMPRSS2, BSG/CD147
and
CTSB
expression compared with negative cases. COVID-19 patients’ age negatively affected
ACE2
expression.
MX1
and
MX2
were higher in COVID-19 patients. A negative trend for
MX1
and
MX2
was observed as patients’ age increased. Principal Component Analysis determined that
ACE2
,
MX1
,
MX2,
and
BSG/CD147
expression was able to cluster non-COVID-19 and COVID-19 individuals. Multivariable regression showed that
MX1
expression significantly increased for each unit of viral load increment. Altogether, these findings support differences in
ACE2
,
MX1
,
MX2,
and
BSG/CD147
expression between COVID-19 and non-COVID-19 patients and point out to MX1 as a critical responder in SARS-CoV-2 infection.
Nuclear transport and vesicle trafficking are key cellular functions involved in the pathogenesis of RNA viruses. Among other pleiotropic effects on virus-infected host cells, ivermectin (IVM) inhibits nuclear transport mechanisms mediated by importins and atorvastatin (ATV) affects actin cytoskeleton-dependent trafficking controlled by Rho GTPases signaling. In this work, we first analyzed the response to infection in nasopharyngeal swabs from SARS-CoV-2-positive and -negative patients by assessing the gene expression of the respective host cell drug targets importins and Rho GTPases. COVID-19 patients showed alterations in KPNA3, KPNA5, KPNA7, KPNB1, RHOA, and CDC42 expression compared with non-COVID-19 patients. An in vitro model of infection with Poly(I:C), a synthetic analog of viral double-stranded RNA, triggered NF-κB activation, an effect that was halted by IVM and ATV treatment. Importin and Rho GTPases gene expression was also impaired by these drugs. Furthermore, through confocal microscopy, we analyzed the effects of IVM and ATV on nuclear to cytoplasmic importin α distribution, alone or in combination. Results showed a significant inhibition of importin α nuclear accumulation under IVM and ATV treatments. These findings confirm transcriptional alterations in importins and Rho GTPases upon SARS-CoV-2 infection and point to IVM and ATV as valid drugs to impair nuclear localization of importin α when used at clinically-relevant concentrations.
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