Chimeric viruses between Rocio and West Nile: the role for Rocio prM-E proteins in virulence and inhibition of interferon-α/β signaling

Abstract

Mosquito-transmitted flavivirus Rocio (ROCV) was responsible for an outbreak of encephalitis in the Ribeira Valley, located in the south coast of Sao Paulo State, Brazil, in 1975–1976. ROCV also causes fatal encephalitis in adult mice. Seroprevalence studies in humans, horses and water buffaloes in different regions of Brazil have suggested that ROCV is still circulating in the country, indicating the risk of re-emergence of this virus. West Nile virus (WNV) is also a mosquito-transmitted encephalitic flavivirus, however, WNV strains circulating in Australia have not been associated with outbreaks of disease in humans and exhibit low virulence in adult mice. To identify viral determinants of ROCV virulence, we have generated reciprocal chimeric viruses between ROCV and the Australian strain of WNV by swapping structural prM and E genes. Chimeric WNV containing ROCV prM-E genes replicated more efficiently than WNV or chimeric ROCV containing WNV prM-E genes in mammalian cells, was as virulent as ROCV in adult mice, and inhibited type I IFN signaling as efficiently as ROCV. The results show that ROCV prM and E proteins are major virulence determinants and identify unexpected function of these proteins in inhibition of type I interferon response.

CCR2 Plays a Protective Role in Rocio Virus–Induced Encephalitis by Promoting Macrophage Infiltration Into the Brain

“…However, it is still unclear how the virus is able to invade the CNS. Although our recent study has shown that the prM-E proteins of ROCV are responsible for neuroinvasion of ROCV and mortality in C57BL/6 mice [21], the exact residues in these proteins and the mechanisms responsible for neuropathogenesis of ROCV infection are still unknown. It is worth noting that ROCV was readily detected in olfactory bulbs 3 days after infection, suggesting that this may be a possible route for ROCV invasion into the CNS.…”

“…ROCV (SPH 34675 strain) was passaged on Aedes albopictus (C6/36) cells and titrated by a plaque assay on BHK-21 cells as previously described [21].…”

Determinants of Zika virus host tropism uncovered by deep mutational scanning

“…The above DMS DNA amplicon was then used in equimolar amount with other ZIKV cDNA fragments and a linker fragment containing either mammalian CMV 12,16,17,19,20 or insect OpIE2 18 promoters in a CPER reaction to produce infectious DNA library as previously described 12 . The CPER-assembled infectious DNA library containing the CMV promoter was then transfected into Vero cells while the CPER-assembled infectious DNA library containing the OpIE2 promoter was transfected into C6/36 cells.…”

Ilheus and Saint Louis encephalitis viruses elicit cross-protection against a lethal Rocio virus challenge in mice

“…The disease was mainly characterized by an acute onset of fever and headache, in addition to clinical signs and symptoms of central nervous system (CNS) involvement such as meningeal irritation, consciousness alterations and motor impairment [ 4 ]. The ability of ROCV to inhibit alpha/beta interferon (IFN-α/β) signaling may determine viral pathogenicity [ 5 ]. Surprisingly, no further cases of ROCV infection have been reported after this outbreak; however, serological surveys have suggested that unreported infections with ROCV among humans and animals in different regions of Brazil are still occurring [ 6 – 9 ].…”