Silencing the alarms: Innate immune antagonism by rotavirus NSP1 and VP3.
The innate immune response involves a broad array of pathogen sensors that stimulate the production of interferons (IFNs) to induce an antiviral state. Rotavirus, a significant cause of childhood gastroenteritis and a member of the Reoviridae family of segmented, double-stranded RNA viruses, encodes at least two direct antagonists of host innate immunity: NSP1 and VP3. NSP1, a putative E3 ubiquitin ligase, mediates the degradation of cellular factors involved in both IFN induction and downstream signaling. VP3, the viral capping enzyme, utilizes a 2H-phosphodiesterase domain to prevent activation of the cellular oligoadenylate synthase (OAS)/RNase L pathway. Computational, molecular, and biochemical studies have provided key insights into the structural and mechanistic basis of innate immune antagonism by NSP1 and VP3 of group A rotaviruses (RVA). Future studies with non-RVA isolates will be essential to understand how other rotavirus species evade host innate immune responses.
Rotavirus Molecular Biology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Marco
M
Morelli
Rotavirus Molecular Biology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kristen M
KM
Ogden
Rotavirus Molecular Biology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jpattn76@vt.edu.
John T
JT
Patton
D036022:Capsid Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D007113:Immunity, Innate; D012401:Rotavirus / Q000276:immunology* / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
D036022:Capsid Proteins; C442546:VP3 protein, Rotavirus; D017361:Viral Nonstructural Proteins; C104282:nsp1 protein, Rotavirus
Innate immunity; Interferon signaling pathway; NF-κB; OAS/RNase L pathway; Rotavirus; Viral E3 ubiquitin ligase; Viral phosphodiesterase; β-TrCP