Abstract
Mayaro virus (MAYV) manipulates cell machinery to successfully replicate. Thus, identifying host proteins implicated in MAYV replication represents an opportunity to discover potential antiviral targets. PIM kinases are enzymes that regulate essential cell functions and also appear to be critical factors in the replication of certain viruses. In this study we explored the consequences of PIM kinase inhibition in the replication of MAYV and other arboviruses. Cytopathic effects or viral titers in samples from MAYV-, Chikungunya-, Una- or Zika-infected cells treated with PIM kinase inhibitors were evaluated using an inverted microscope or plaque-forming assays. The expression of viral proteins E1 and nsP1 in MAYV-infected cells was assessed using an immunofluorescence confocal microscope or Western blot. Our results revealed that PIM kinase inhibition partially prevented MAYV-induced cell damage and also promoted a decrease in viral titers for MAYV, UNAV and ZIKV. The inhibitory effect of PIM kinase blocking was observed for each of the MAYV strains tested and also occurred as late as 8 h post infection (hpi). Finally, PIM kinase inhibition suppressed the expression of MAYV E1 and nsP1 proteins. Taken together, these findings suggest that PIM kinases could represent an antiviral target for MAYV and other arboviruses.
Highlights
Mayaro virus (MAYV) is an emerging arbovirus within the Alfavirus genus that belongs to the Togaviridae family [1]
Primary human dermal fibroblasts (HDFs) from adults (PCS-201-012), Vero-E6 (CRL1586), Vero (CCL-81) and HeLa cells were grown in Minimal Essential Medium (MEM) or Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 2 mM of L-Glutamine and 1% penicillinstreptomycin antibiotic solution
The virus strains used in this study were as follows: Mayaro (MAYV AVR0565, Peru; MAYV TRVL 4675, Trinidad and Tobago; MAYV Guyane, French Guiana) [30]; Una (UNAV, BT-1495-3, Bocas del Toro, Panama) [31] (all previous strains were acquired from the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA) at the University of Texas Medical Branch (UTMB), Galveston, TX, USA); Chikungunya (CHIKV, Panama_256137) [32]; and Zika (ZIKV, 259249)
Summary
Mayaro virus (MAYV) is an emerging arbovirus within the Alfavirus genus that belongs to the Togaviridae family [1]. Cellular kinases are vital enzymes that regulate an array of important cell activities and play a crucial role in the replication of diverse families of viruses [12,13,14]. Using zebrafish as an in vivo infection model, Pereiro and collaborators found that treating with pan-PIM kinase inhibitors SGI1776, INCB053914 and AZD1208 blocked the replication of spring viraemia of carp virus (SVCV) [29]. Together, these previous observations indicate that PIM kinases may be important factors implicated in viral replication and could serve as potential antiviral targets. We analyzed the impact of PIM kinase inhibition on the replication of MAYV and other emerging arboviruses
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