Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis

: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. ORF6 plays key roles in interferon antagonism and viral pathogenesis by interfering with nuclear import and specifically the translocation of IRF and STAT transcription factors. Additionally, ORF6 inhibits cellular mRNA export, resulting in the remodeling of the host cell proteome, and regulates viral protein expression. Interestingly, the ORF6:D61L mutation that emerged in the Omicron BA.2 and BA.4 variants exhibits reduced interactions with Nup98-Rae1 and consequently impairs immune evasion. Our findings highlight the role of ORF6 in antagonizing innate immunity and emphasize the importance of studying the immune evasion strategies of SARS-CoV-2

The epidemiology of enterococci

The enterococci are emerging as a significant cause of nosocomial infections, accounting for approximately 10 % of hospital acquired infections. They are found as normal inhabitants of the human gastrointestinal tract, but may also colonize the oropharynx, vagina, perineal region and soft tissue wounds of asymtomatic patients. Until recently, evidence indicated that most enterococcal infections arose from patients' own endogenous flora. Recent studies, however, suggest that exogeneous acquisition may occur and that person-to-person spread, probably on the hands of medical personnel, may be a significant mode of transmission of resistant enterococci within the hospital. The use of broad-spectrum antibiotics, especially cephalosporins, is another major factor in the increasing incidence of enterococcal infections. These findings suggest that barrier precautions, as applied with other resistant nosocomial pathogens, along with more judicial use of antibiotics may be beneficial in preventing nosocomial spread of resistant enterococci.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47899/1/10096_2005_Article_BF01963631.pd