Higher Cytopathic Effects of a Zika Virus Brazilian Isolate from Bahia Compared to a Canadian-Imported Thai Strain

Abstract

Zika virus (ZIKV) is an emerging pathogen from the Flaviviridae family. It represents a significant threat to global health due to its neurological and fetal pathogenesis (including microcephaly and congenital malformations), and its rapid dissemination across Latin America in recent years. The virus has spread from Africa to Asia, the Pacific islands and the Americas with limited knowledge about the pathogenesis associated with infection in recent years. Herein, we compared the ability of the Canadian-imported Thai strain PLCal_ZV and the Brazilian isolate HS-2015-BA-01 from Bahia to produce infectious ZIKV particles and cytopathic effects in a cell proliferation assay. We also compared the intracellular viral RNA accumulation of the two strains by quantitative RT-PCR (reverse transcription polymerase chain reaction) analyses. Our observations show that HS-2015-BA-01 is more cytopathic than PLCal_ZV in proliferation assays in Vero, Human Embryonic Kidney HEK 293T and neuroblastoma SH-SY5Y cells. Quantitative RT-PCR shows that the level of viral RNA is higher with HS-2015-BA-01 than with PLCal_ZV in two cell lines, but similar in a neuroblastoma cell line. The two strains have 13 amino acids polymorphisms and we analyzed their predicted protein secondary structure. The increased cytopathicity and RNA accumulation of the Brazilian ZIKV isolate compared to the Thai isolate could contribute to the increased pathogenicity observed during the Brazilian epidemic.

Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells

“…Our data suggests that strain-dependent differences in viral replicative fitness are highly dependent on both cell type and the MOI used, which may explain some of these discrepancies in the literature. For example, several groups have demonstrated enhanced infectivity and replication by contemporary American ZIKV isolates, similar to what we observed herein at high MOI [39,40]. In contrast, other groups have shown that African lineage ZIKV isolates display higher infectivity and increased cytopathicity in cell culture than Asian lineage isolates when low MOIs (≤1) were used, where few cells are predicted to be infected, similar to what we observed herein [41,42,43,44].…”

Potential neuroprotective and anti-inflammatory effects provided by omega-3 (DHA) against Zika virus infection in human SH-SY5Y cells

“…SH-SY5Y cells are widely used as an important model for approaches focused on neuronal cells physiology and neurological diseases and several studies have provided very pertinent biological and pharmacological findings using SH-SY5Y as a neuronal-like in vitro model [29][30][31][32][33][34] . In our work, we could observe that ZIKV decreased SH-SY5Y cells viability in a time-dependent manner, corroborating with other studies that uses the same cell line 31,33 . At initial times, as 24 and 48 hours of infection, ZIKV maintained cell viability around 100%.…”

Whole genome sequencing, variant analysis, phylogenetics, and deep sequencing of Zika virus strains

“…How these high- and low-frequency variants contribute to viral evolution, host specificity, and/or the host innate and adaptive immune response over time is largely unknown and warrants additional investigation. However, one study reported an increase in cytopathic effects associated with the A1263V substitution among other mutations in a Brazilian strain collected during the recent ZIKV outbreak 33 . A resolved three-dimensional protein crystal structure of the ZIKV capsid (C) protein shows that the I81 residue, for which we identified a minor variant, contributes to hydrophobic interactions within the protein 34 .…”