Mayora-Neto, M. | bioRxiv Science

bioRxiv2021

Pseudotyped Bat Coronavirus RaTG13 is efficiently neutralised by convalescent sera from SARS-CoV-2 infected Patients

RaTG13 is a close relative of SARS-CoV-2, the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, sharing 96% sequence similarity at the genome-wide level. The spike receptor binding domain (RBD) of RaTG13 contains a large number of amino acid substitutions when compared to SARS-CoV-2, likely impacting affinity for the ACE2 receptor. Antigenic differences between the viruses are less well understood, especially whether RaTG13 spike can be efficiently neutralised by antibodies generated from infection with, or vaccination against, SARS-CoV-2. Using RaTG13 and SARS-CoV-2 pseudotypes we compared neutralisation using convalescent sera from previously infected patients as well as vaccinated healthcare workers. Surprisingly, our results revealed that RaTG13 was more efficiently neutralised than SARS-CoV-2. In addition, neutralisation assays using spike chimeras and mutants harbouring single amino acid substitutions within the RBD demonstrated that both spike proteins can tolerate multiple changes without dramatically reducing how efficiently they are neutralised. Moreover, introducing the 484K mutation into RaTG13 resulted in increased neutralisation, in contrast to the same mutation in SARS-CoV-2 (E484K). This is despite E484K having a well-documented role in immune evasion in variants of concern (VOC) such as B.1.351 (Beta). These results indicate that the immune-escape mutations found in SARS-CoV-2 VOCs might be driven by strong antibody pressures, and that the future spill-over of RaTG13 and/or related sarbecoviruses could be mitigated using current SARS-CoV-2-based vaccination strategies.

microbiology↗

bioRxiv2021

Reservoir host studies of Lloviu virus: first isolation, sequencing and serology in Schreiber's bats in Europe

IntroductoryFiloviruses are prime examples of emerging human pathogens that are transmitted to humans by zoonotic spillover events. Since their initial discovery, filovirus outbreaks have occured with increasing frequency and intensity. There is an urgent need to better understand their enzootic ecology and pathogenic potential, given recent zoonotic virus spillover events including the 2013-2016 West African Ebola virus (EBOV) epidemic. Several novel filoviruses have been discovered with a markedly wider geographic distribution than previously described. One of these novel filoviruses, Lloviu virus (LLOV), was first identified in 2002 in Schreibers bats (Miniopterus schreibersii) in Spain, Portugal, and southern France. Subsequently, in 2016, LLOV was detected during the passive monitoring of bats in Hungary. Here we report the first isolation of infectious Lloviu virus; from the blood of an asymptomatic Schreibers bat, subsequently cultivated in the Miniopterus sp. kidney cell line SuBK12-08. We also show that LLOV is able to infect monkey and human cells, suggesting that LLOV might have spillover potential. We performed a multi-year surveillance of LLOV and detected LLOV RNA in both deceased and asymptomatic live animals as well as in coupled ectoparasites from the families Nycteribiidae and Ixodidae. We present data on the natural infection and seropositivity of Schreibers bats and provide novel LLOV genomic sequence information from a bat host and an arthropod parasite. Our data support the role of bats, specifically Miniopterus schreibersii as natural reservoirs for the LLOV filovirus in Europe. We also suggest that bat-associated parasites might play a role in the natural ecology of filoviruses in temperate climate regions compared to filoviruses in the tropics. These results raise the possibility of cross-species transmission events via bat-human interactions.

microbiology↗