Severe COVID-19 is a biphasic illness, with an initial viral replication phase, followed by a cascade of inflammatory events. Progression to severe disease is predominantly a function of the inflammatory cascade, rather than viral replication per se. This understanding can be effectively translated to changing our approach in managing the disease. The natural course of disease offers us separate windows of specific time intervals to administer either antiviral or immunomodulatory therapy. Instituting the right attack at the right time would maximize the benefit of treatment. This concept must also be factored into studies that assess the efficacy of antivirals and immunomodulatory agents against COVID-19.
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http://dx.doi.org/10.1093/jac/dkaa442 | DOI Listing |
Cell Mol Life Sci
January 2025
Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (CISA-INIA-CSIC), Valdeolmos, Madrid, Spain.
Cyclic GMP-AMP synthase (cGAS) is a DNA sensing cellular receptor that induces IFN-I transcription in response to pathogen and host derived cytosolic DNA and can limit the replication of some RNA viruses. Some viruses have nonetheless evolved mechanisms to antagonize cGAS sensing. In this study, we evaluated the interaction between Bluetongue virus (BTV), the prototypical dsRNA virus of the Orbivirus genus and the Sedoreoviridae family, and cGAS.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.
Viral infections are characterized by dispersal from an initial site to secondary locations within the host. How the resultant spatial heterogeneity shapes within-host genetic diversity and viral evolutionary pathways is poorly understood. Here, we show that virus dispersal within and between the nasal cavity and trachea maintains diversity and is therefore conducive to adaptive evolution, whereas dispersal to the lungs gives rise to population heterogeneity.
View Article and Find Full Text PDFmBio
January 2025
Department of Infectious Diseases and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
The human cellular cytidine deaminases APOBEC3s (A3s) inhibit virion infectivity factor (Vif)-deficient HIV-1 replication. However, virus-encoded Vifs abolish this defense system by specifically recruiting A3s to an E3 ubiquitin ligase complex to induce their degradation. The highly conserved Vif PPLP motif is critical for the Vif-mediated antagonism of A3s and is believed to be important for Vif multimerization.
View Article and Find Full Text PDFJ Virol
January 2025
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
Porcine epidemic diarrhea virus (PEDV), as a type of Alphacoronavirus causing acute diarrhea and high death rate among sucking piglets, poses great financial damage to the swine industry. Nevertheless, the molecular mechanism whereby PEDV enters host cells is unclear, limiting the development of PED vaccines and anti-PEDV agents. The present study found that the host protein ribonuclease kappa (RNASEK) was regulated by USF2, a transcription factor, and facilitated the PEDV replication.
View Article and Find Full Text PDFJ Virol
January 2025
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, USA.
Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with Kaposi's sarcoma and B cell malignancies. Like all herpesviruses, KSHV contains conserved envelope glycoproteins (gps) involved in virus binding, entry, assembly, and release from infected cells, which are also targets of the immune response. Due to the lack of a reproducible animal model of KSHV infection, the precise functions of the KSHV gps during infection are not completely known.
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