ABSTRACT The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 (clade 2.3.4.4b, genotype B3.13) in dairy cattle presents substantial challenges to the agricultural sector and public health. Mechanistic studies of infection and transmission in cattle have proven difficult due to animal handling restrictions and the limited availability of established cell culture models. Primary bovine embryonic fibroblasts (BeEFs) were isolated and investigated here as a model to study influenza A virus (IAV) infection dynamics. We compared sialylation profiles , infectious virus production, viral replication, and plaque morphology in BeEFs following infection with the bovine HPAI H5N1 and an earlier 2.3.4.4b genotype (B1.1) isolated in 2022. The data presented here demonstrate increased expression of α-2,3 sialic acids compared to α-2,6 sialic acids in BeEFs , similar to sialylation profiles previously reported in bovine mammary tissue . These data also display increased viral fi...
#SARS-CoV-2 Error Catastrophe Under #Molnupiravir: #Mutagenic Enhancement Enables Viral #Persistence with Impaired Fitness
Abstract Molnupiravir induces mutations that render severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication-competent through error catastrophe mechanisms . Previous studies showed no resistant virus emergence during prolonged molnupiravir treatment, with no resistant variants reported . However, these approaches were limited by genetic uniformity at passage initiation. To investigate viral population dynamics under enhanced genetic diversity, we employed mutagenic pre-treatment using 5-fluorouracil (5-FU) and favipiravir to generate diverse quasi-species populations before molnupiravir selection pressure. Viral populations were treated with stepwise increasing molnupiravir concentrations (10 μM ⟶ 25 μM ⟶ 40 μM) over ten serial passages . Viral detectability, plaque morphology, and mutation accumulation were analyzed using molecular and sequencing approaches . Only high-concentration favipiravir (1000 μM) pre-treatment maintained detectable viral RNA through ten ...