Inhibition of Vesicular Stomatitis Virus Replication in Dexamethasone-Treated L929 Cells

Abstract

We previously demonstrated that dexamethasone treatment of L929 cells inhibited plaque formation by vesicular stomatitis virus (VSV), encephalomyocarditis virus, or vaccinia virus. We now have characterized the antiviral effects of glucocorticoids in L929 cells. Dexamethasone did not directly inactivate VSV nor did steroid treatment of L929 cells affect virion adsorption or penetration. The VSV yield in L929 cells treated with dexamethasone for a period of only 4 or 8 hr was decreased by 50% when cells were infected the day following steroid treatment. Treating L929 cells with dexamethasone for a longer period resulted in greater inhibitions of virus synthesis. Interferon activity (less than 5 units/ml) was not detected in L929 cell culture fluids and cell sonicates from steroid-treated cells and the addition of antiserum to murine alpha/beta-interferon had no effect on the ability of dexamethasone to inhibit VSV replication. Dexamethasone treatment of L929 cells did not induce the production of double-stranded RNA-dependent protein kinase but did result in a slight elevation of 2-5A oligoadenylate synthetase activity, two enzymatic activities associated with the antiviral state induced by interferon. However, the elevated 2-5A synthetase activity was not associated with an inhibition of VSV RNA accumulation in dexamethasone-treated L929 cells. By contrast, the synthesis of all five VSV proteins was reduced by 50-75% in dexamethasone-treated L929 cells as early as 4 hr after infection. Thus, the dexamethasone-mediated inhibition of VSV replication in L929 cells is associated with decreased production of VSV structural proteins.

Non-Targeted Metabolomic Analysis of Chicken Kidneys in Response to Coronavirus IBV Infection Under Stress Induced by Dexamethasone

“…Differences in timing and dose underlie many of the inconsistent and sometimes conflicting results across studies of GC therapy (Cain and Cidlowski, 2020). GCs are often used in combination with antiviral drugs to counteract painful inflammation and are known to inhibit the replication of some viruses (Lancz et al, 1990;Kim et al, 2017), However, this approach is controversial, because GC treatment has been suggested to increase the viral yield and susceptibility, thereby increasing lung lesions and increasing or prolonging shedding of viruses, such as SARS-CoV (Li et al, 2003), SIVs (Ali et al, 2013), HSV-1 (Erlandsson et al, 2002;Hara et al, 2009;Du et al, 2012;Pechan et al, 2014), MMTV (Parks et al, 1974;Indik et al, 2007), retroviruses (Solodushko et al, 2009), PRRSV-1 (Singleton et al, 2018) and FFV (Lee and Shin, 2018). Consequently, GC use is often hampered by the onset of adverse effects or resistance (Petta et al, 2016).…”

Plant and Animal Steroids a New Hope to Search for Antiviral Agents

“…Most of the assayed compounds exhibit better SI than 28-homocastasterone (20) which possesses the basic steroidal skeleton of all the synthetic compounds ( Table 3). Compounds 21, 28 and 29 were active against all the viruses assayed: HSV-1, HSV-2, measles virus (MV) and JUNV.…”

“…The inhibitory action of 6 against VSV was attributed to inhibition of viral protein synthesis and was not associated to interferon induction [20].…”

“…It is known that natural BRs (for example 28-homocastasterone (20), a very active phytohormone, posses a diol with a 22R, 23R configuration at the side chain. Our findings indicate that analogues having the opposite unnatural configuration at these positions usually show an enhanced activity (compare 26 to 27, or 22 to 23).…”