Meyers, K. | bioRxiv Science

bioRxiv2022

SARS-CoV-2 Omicron BA.2.12.1, BA.4, and BA.5 subvariants evolved to extend antibody evasion

SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged dramatically to become dominant in the United States and South Africa, respectively1,2. These novel subvariants carrying additional mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain3. The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.

microbiology↗

bioRxiv2018

Did a novel virus contribute to late blight epidemics?

Phytophthora infestans is the causal agent of potato and tomato late blight. In this study, we characterized a novel RNA virus, Phytophthora infestans RNA virus 2 (PiRV-2). The PiRV-2 genome is 11,170 nt and lacks a polyA tail. It contains a single large open reading frame (ORF) with short 5- and 3-untranslated regions. The ORF is predicted to encode a polyprotein of 3710 aa (calculated molecular weight 410.94 kDa). This virus lacks significant similarity to any other known viruses, even in the conserved RNA-dependent RNA polymerase region. Comparing isogenic strains with or without the virus demonstrated that the virus stimulated sporangia production in P. infestans and appeared to enhance its virulence. Transcriptome analysis revealed that it achieved sporulation stimulation likely through down-regulation of ammonium and amino acid intake in P. infestans. This virus was faithfully transmitted through asexual reproduction. Survey of PiRV-2 presence in a P. infestans collection found it in most strains in the US-8 lineage, a very successful clonal lineage of P. infestans in North America. We suggest that PiRV-2 may have contributed to its success, raising the intriguing possibility that a potentially hypervirulent virus may contribute to late blight epidemics.\n\nAuthor SummaryPotato late blight, the notorious plant disease behind the Irish Potato Famine, continues to pose a serious threat to potato and tomato production worldwide. While most studies on late blight epidemics focuses on pathogen virulence, host resistance, environmental factors and fungicide resistance, we present evidence in this study that a virus infecting the causal agent, Phytophthora infestans, may have played a role. We characterized a novel RNA virus, Phytophthora infestans RNA virus 2 (PiRV-2) and examined its effects on its host. By comparing identical P. infestans strains except with or without the virus, we found that PiRV-2 stimulated sporulation of P. infestans (a critical factor in late blight epidemics) and increased its virulence. We also profiled gene expression in these strains and identified potential molecular mechanisms through which PiRV-2 asserted its sporulation stimulation effect. In a survey of PiRV-2 presence in a P. infestans collection, we found PiRV-2 in most isolates of the US-8 clonal lineage, a very successfull ineage that dominated potato fields in North America for several decades. We suggest that PiRV-2 may have contributed to its success. Our findings raise the intriguing possibility that a potentially hypervirulent virus may contribute to late blight epidemics.

pathology↗