CHIKV strains Brazil (wt) and Ross (lab-adapted) differ with regard to cell host range and antiviral sensitivity and show CPE in human glioblastoma cell lines U138 and U251

Abstract

Chikungunya virus (CHIKV), a (re)emerging arbovirus, is the causative agent of chikungunya fever. To date, no approved vaccine or specific antiviral therapy are available. CHIKV has repeatedly been responsible for serious economic and public health impacts in countries where CHIKV epidemics occurred. Antiviral tests in vitro are generally performed in Vero-B4 cells, a well characterised cell line derived from the kidney of an African green monkey. In this work we characterised a CHIKV patient isolate from Brazil (CHIKV Brazil ) with regard to cell affinity, infectivity, propagation and cell damage and compared it with a high-passage lab strain (CHIKV Ross ). Infecting various cell lines (Vero-B4, A549, Huh-7, DBTRG, U251, and U138) with both virus strains, we found distinct differences between the two viruses. CHIKV Brazil does not cause cytopathic effects (CPE) in the human hepatocarcinoma cell line Huh-7. Neither CHIKV Brazil nor CHIKV Ross caused CPE on A549 human lung epithelial cells. The human astrocyte derived glioblastoma cell lines U138 and U251 were found to be effective models for lytic infection with both virus strains and we discuss their predictive potential for neurogenic CHIKV disease. We also detected significant differences in antiviral efficacies regarding the two CHIKV strains. Generally, the antivirals ribavirin, hydroxychloroquine (HCQ) and T-1105 seem to work better against CHIKV Brazil in glioblastoma cells than in Vero-B4. Finally, full genome analyses of the CHIKV isolates were done in order to determine their lineage and possibly explain differences in tissue range and antiviral compound efficacies. Supplementary Information The online version contains supplementary material available at 10.1007/s11262-022-01892-x.

Antiviral and Virucidal Activities of Uncaria tomentosa (Cat’s Claw) against the Chikungunya Virus

“…Several in vitro studies have successfully used the Vero cell lineage since they are very susceptible to CHIKV infection even at low MOI at 48 h post-infection (p.i) [ 42 , 43 , 44 ]. Initially, we determined the ECSA strain cytotoxicity profile after 48 h p.i.…”

In Silico Drug Repurposing Uncovered the Antiviral Potential of the Antiparasitic Drug Oxibendazole Against the Chikungunya Virus

“…Different CHIKV strains present different replication kinetics, lead to different pathogenesis, and result in different disease severities. Accordingly, similar treatments can show different antiviral efficacies against different CHIKV strains in vitro and in vivo. , Consequently, we further investigated the antiviral effects of OBZ against a Brazilian isolate (BRA/RJ/18; ECSA genotype), which is a more virulent strain and is possibly more associated with chronic infections . Although the drug CQ showed a decreased activity against this virulent strain (48.5%), OBZ exhibited a strain-independent antiviral activity and maintained a similar inhibition rate (61.8%).…”

Cell-Type-Dependent Role for nsP3 Macrodomain ADP-Ribose Binding and Hydrolase Activity during Chikungunya Virus Infection

“…However, recent outbreaks of CHIKV infection have included a variety of neurologic complications including encephalomyelitis, Guillain-Barre syndrome, neonatal hypotonia, and neuro-ocular disease [2]. Studies of CHIKV neurotropism in mice and macaques have shown preferential infection of astrocytes rather than neurons [3,4] and in vitro studies confirm efficient replication and cytopathic effects in astrocytes and glial cells [5][6][7]. Astrocyte tropism was also observed during in vivo stereotaxic delivery of a CHIKV-pseudotyped vector to adult rat brain [8].…”