Host Factors in Coronavirus Replication

Abstract

Coronaviruses are pathogens with a serious impact on human and animal health. They mostly cause enteric or respiratory disease, which can be severe and life threatening, e.g., in the case of the zoonotic coronaviruses causing severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in humans. Despite the economic and societal impact of such coronavirus infections, and the likelihood of future outbreaks of additional pathogenic coronaviruses, our options to prevent or treat coronavirus infections remain very limited. This highlights the importance of advancing our knowledge on the replication of these viruses and their interactions with the host. Compared to other +RNA viruses, coronaviruses have an exceptionally large genome and employ a complex genome expression strategy. Next to a role in basic virus replication or virus assembly, many of the coronavirus proteins expressed in the infected cell contribute to the coronavirus-host interplay. For example, by interacting with the host cell to create an optimal environment for coronavirus replication, by altering host gene expression or by counteracting the host's antiviral defenses. These coronavirus-host interactions are key to viral pathogenesis and will ultimately determine the outcome of infection. Due to the complexity of the coronavirus proteome and replication cycle, our knowledge of host factors involved in coronavirus replication is still in an early stage compared to what is known for some other +RNA viruses. This review summarizes our current understanding of coronavirus-host interactions at the level of the infected cell, with special attention for the assembly and function of the viral RNA-synthesising machinery and the evasion of cellular innate immune responses.

Cyclophilins and cyclophilin inhibitors in nidovirus replication

“…Among these nsps are subunits containing RNA-dependent RNApolymerase and helicase functions, key players in the enzyme complex responsible for viral RNA synthesis. Together with recruited host cell proteins, nidovirus nsps form membrane-associated replication and transcription complexes (Gosert et al, 2002;Hagemeijer et al, 2012;Pedersen et al, 1999;van Hemert et al, 2008avan Hemert et al, , 2008b) that localize to a network of virus-induced structures, typically including doublemembrane vesicles, in the perinuclear region of the infected cell (reviewed in de Wilde et al, 2017b;Romero-Brey and Bartenschlager, 2016;van der Hoeven et al, 2016). A nested set of subgenomic (sg) mRNAs is produced to express the structural and accessory proteins that are encoded downstream of the nidovirus replicase gene (Pasternak et al, 2006;Sawicki et al, 2007;Snijder et al, 2013;Sola et al, 2011).…”

The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

“…FIPV infection has a complex immunopathogenesis, a feature shared by other coronavirus infections (de Wilde et al, 2017), and has become one of the most researched infectious diseases of cats since its discovery over a half century ago (Kipar and Meli, 2014;Pedersen, 2014aPedersen, , 2014bTekes and Thiel, 2016). Despite these advances, modern treatment options for FIP remain palliative and vaccines have proven either unsafe or ineffective (Pedersen, 2014b).…”

COVID-19, una emergencia de salud pública mundial

“…Los coronavirus se pueden diferenciar en 4 géneros: alfa, beta, delta y gamma, de los cuales hasta el momento se sabe que los coronavirus de tipo alfa y beta infectan a los humanos 5 , provocando enfermedades que van desde el resfriado común hasta afecciones más graves, como el síndrome respiratorio de Oriente Medio (MERS-CoV) y el síndrome respiratorio agudo severo (SARS-CoV), que causó miles de muertes en 2002 6,7 . Cuatro de los HCoV (HCoV 229E, NL63, OC43 y HKU1) son endémicos en todo el mundo y representan del 10 al 30% de las infecciones del tracto respiratorio superior en adultos 5 .…”

“…El ARN genómico presenta modificaciones como poliadenilaciones en la región 3' terminal; en cambio, la región 5' terminal contiene una estructura tipo cap 12 . Dentro de este ARN existen múltiples marcos de lectura abiertos (6)(7)(8)(9)(10)(11). El primer ORF codifica para aproximadamente 16 proteínas no estructurales, mientras que los ORF restantes codifican para proteínas accesorias y no estructurales (fig.…”