Biases in Cap-Snatching of Host RNA by Influenza A Virus
To co-opt host translational machinery and evade detection of non-self RNAs by host cells, influenza A virus (IAV) “snatches” 5′ RNA caps and short nucleotide sequences from host RNAs. Until now, scientists considered cap-snatching a random process. Clohisey et al. (e01720-19) discovered biased snatching of host RNAs, including those associated with small nuclear RNA (snRNA) transcription. They also showed that IAV avoids transcripts encoding host ribosomal proteins, which are required for viral replication. These findings provide a new perspective for this host-pathogen interaction.
Pathways highlighted in cap-snatching of host RNA by IAV.
A Chronic Hepatitis C-Like Virus Animal Model That Recapitulates CD8 T Cell Immune Subversion
Hepatitis C virus (HCV) establishes persistent viral infections in humans by subverting host CD8 T cell immunity. Hartlage et al. (e00035-20) found that a persistent HCV-like virus from rats induces a robust CD8 T cell response that is dysfunctional and thus unable to control infection. Rapid, short-term treatment of rats with a potent antiviral partially restored CD8 T cell functionality but led to selection of an immune escape mutant. These findings highlight the relevance of this surrogate model for investigating fundamental aspects of HCV infection, immunity, and vaccine development.
Virus infection, pathology, and CD8 T cell response in laboratory rats.
Reovirus Removes IKK Subunits To Block NF-κB Signaling
Viruses must antagonize the innate immune response for successful infection of host cells. Using RNA sequencing, McNamara and Danthi (e00382-20) found that reovirus potently activates the innate immune response in cells, but expression of transcription factor NF-κB targets is underrepresented. Strong agonists failed to activate NF-κB-dependent gene expression in reovirus-infected cells. Loss of an upstream kinase complex during reovirus infection blocked NF-κB-dependent gene expression. This work uncovers a novel mechanism by which reovirus modulates intracellular signaling to sustain a proviral cellular environment.
IKKβ is lost following reovirus infection.
Identification and Characterization of Western Epstein-Barr Virus Strains That Defy the Dogma
Epstein-Barr virus (EBV)-infected cells produce virions during lytic replication or undergo viral latency. Classically, while epithelial cells produce virus, B cells are latently infected. Certain isolates, particularly those found in Asian nasopharyngeal carcinomas, produce virus in infected B cells. Similarly, EBV-associated B-cell tumors frequently contain cells that replicate virus. Delecluse et al. (e01918-19) isolated new strains in Western patients that strongly replicate in B cells and studied their sensitivity to various inducers and inhibitors of replication. One of these viruses is available as a bacterial artificial chromosome that can be used to study replication in B cells.
Electron micrograph showing virus production in B cells infected by a virus isolated from a European patient.
Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation
Respiratory syncytial virus (RSV) is responsible for approximately 80% of all lower respiratory tract infections in children. Li et al. (e00113-20) found that RSV decreases expression of the long noncoding RNA negative regulator of antiviral response (NRAV) in patients’ sputum specimens. NRAV competed with the vesicle protein Rab5c for the microRNA miR-509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation. This study may facilitate improvement in the exploration of potential noncoding RNA targets for diagnosis and treatment of respiratory virus infections.
Schematic model of the NRAV/miR-509/Rab5c axis in RSV infection.