The C Protein Is Recruited to Measles Virus Ribonucleocapsids by the Phosphoprotein.

Measles virus (MeV), like all viruses of the order Mononegavirales, utilizes a complex consisting of genomic RNA, nucleoprotein, the RNA-dependent RNA polymerase, and a polymerase cofactor, the phosphoprotein (P), for transcription and replication. We previously showed that a recombinant MeV that does not express another viral protein, C, has severe transcription and replication deficiencies, including a steeper transcription gradient than the parental virus and generation of defective interfering RNA. This virus is attenuated in vitro and in vivo However, how the C protein operates and whether it is a component of the replication complex remained unclear. Here, we show that C associates with the ribonucleocapsid and forms a complex that can be purified by immunoprecipitation or ultracentrifugation. In the presence of detergent, the C protein is retained on purified ribonucleocapsids less efficiently than the P protein and the polymerase. The C protein is recruited to the ribonucleocapsid through its interaction with the P protein, as shown by immunofluorescence microscopy of cells expressing different combinations of viral proteins and by split luciferase complementation assays. Forty amino-terminal C protein residues are dispensable for the interaction with P, and the carboxyl-terminal half of P is sufficient for the interaction with C. Thus, the C protein, rather than being an "accessory" protein as qualified in textbooks so far, is a ribonucleocapsid-associated protein that interacts with P, thereby increasing replication accuracy and processivity of the polymerase complex.IMPORTANCE Replication of negative-strand RNA viruses relies on two components: a helical ribonucleocapsid and an RNA-dependent RNA polymerase composed of a catalytic subunit, the L protein, and a cofactor, the P protein. We show that the measles virus (MeV) C protein is an additional component of the replication complex. We provide evidence that the C protein is recruited to the ribonucleocapsid by the P protein and map the interacting segments of both C and P proteins. We conclude that the primary function of MeV C is to improve polymerase processivity and accuracy, rather than uniquely to antagonize the type I interferon response. Since most viruses of the Paramyxoviridae family express C proteins, their primary function may be conserved.

A 15-year review of characteristics and outcomes of patients leaving against medical advice.

PURPOSE: Discharging against medical advice can have significant, detrimental effects on burn patient outcomes as well as higher hospital readmission rates and healthcare expenditures. The goal of this study is to identify characteristics of patients who left against medical advice and suggest solutions to mitigate these factors. Data were collected at our American Burn Association verified Burn Unit over a 15-year period. RESULTS: Between 2007 and 2022, 37 patients were identified as having left against medical advice from the burn unit. The average patient age was 37 years old with 64.9% being male, and 70.2% were identified as having a substance abuse history. The majority (51.4%) had Medicaid or State health insurance, 29.7% had no insurance, and 18.9% had private insurance. The mechanism of injury was most commonly frostbite (43.2%). The majority sustained < 1% total body surface area injuries. Most (83.7%) had social work and/or case management involved during their admission, and all (100%) had their involvement if the length of admission was greater than one day. Over half (59.5%) returned to the ED within 2 weeks with complications. CONCLUSIONS: This study found that patients discharging against medical advice from the burn unit suffered from smaller injuries, often due to cold related injuries. These patients had comorbid substance abuse or psychiatric histories, and the majority had Medicaid or state health insurance. Recruiting interdisciplinary care members, including social work, psychiatry, and addiction medicine, early may help these patients by encouraging completion of their hospital care and setting up crucial follow-up care.