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J Virol. 2016 February 1; 90(3): 1157.
Published online 2016 January 15. doi:  10.1128/JVI.03076-15
PMCID: PMC4719624

Articles of Significant Interest Selected from This Issue by the Editors

The Structure of Human Parechovirus 1 Indicates a Role of the RNA Genome in Virion Assembly

Parechoviruses cause human diseases ranging from respiratory and gastrointestinal disorders to encephalitis. Kalynych et al. (p. 1377–1386) show that a hydrophobic pocket within capsid protein VP1, which can be targeted by antiviral compounds in other picornaviruses, is absent in human parechovirus 1 (HPeV-1), explaining why previous attempts to use these compounds against parechoviruses failed. The HPeV-1 genome is partly icosahedrally ordered. Protein residues involved in RNA binding are conserved among all parechoviruses, suggesting an evolutionarily conserved role of the genome in virion assembly. Therefore, disruption of parechovirus RNA-capsid protein interactions could be a useful antiviral strategy.

figure zjv0031613410001
Interactions of HPeV-1 genomic RNA with the capsid.

Uncovering Viral Entry Factors with Forward Genetics

Entry factors for members of the Bunyaviridae, including Rift Valley fever virus (RVFV), are incompletely understood. Riblett et al. (p. 1414–1423) used a powerful forward-genetics approach to discover a suite of cellular enzymes, including the newly characterized PTAR1 protein, that regulate RVFV binding and entry through the glycosaminoglycan synthesis pathway. While glycosaminoglycans are important for all RVFV isolates tested thus far, dependence on these glycans across other pathogenic members of the Bunyaviridae varies. These results underscore the diversity among bunyaviruses that must be considered in the search for antivirals.

figure zjv0031613410002
Host factors supporting RVFV infection in human cells.

RNA Target Specificity of the Epstein-Barr Virus SM Protein

The Epstein-Barr virus (EBV) SM protein is essential for lytic EBV replication. Thompson et al. (p. 1206–1221) identify the EBV genes that are most highly dependent on SM. Neither affinity for SM nor other sequence characteristics defined the SM-dependent RNA subset, suggesting that while target RNA binding by SM may be required, specific activation by SM is due to differences in inherent properties of individual transcripts. These findings lead to a new model for the mechanism of action of SM and related herpesvirus proteins: they bind many RNAs but enhance accumulation of only those that are intrinsically poorly expressed.

figure zjv0031613410003
RNA-seq analysis of lytic EBV gene expression in the presence and absence of SM protein.

The Small Tumor Antigen of Merkel Cell Polyomavirus Is an Iron-Sulfur Cluster Protein

Merkel cell polyomavirus (MCPyV) small tumor (sT) antigen has emerged as the key oncogenic driver in Merkel cell carcinoma development. Tsang et al. (p. 1544–1556) found that MCPyV sT is a Fe/S cluster protein and show that the conserved Fe/S cluster-coordinating cysteines in MCPyV sT are required for stimulation of viral replication. The discovery of Fe/S clusters in MCPyV sT opens new avenues for studies of structure-activity relationships and identifies sT as a potential drug target for dampening MCPyV infection.

figure zjv0031613410004
Association of 55Fe with MCPyV sT expressed in mammalian cells.

Rescuing Vero Cell-Derived Respiratory Syncytial Virus Infectivity

Candidate live, attenuated respiratory syncytial virus (RSV) vaccines are propagated in Vero cells, where most of the virion attachment (G) glycoprotein is cleaved. As a result, Vero cell-propagated RSV is 5-fold less infectious for primary human airway epithelial (HAE) cells, the natural RSV target. Corry et al. (p. 1311–1320) demonstrate that the G protein is cleaved by cathepsin L, likely during endocytic recycling, and identified a 7-residue cluster that regulates G protein cleavage. Infection of Vero cells with RSV containing a mutation in this cluster yields progeny with 5-fold enhanced infectivity for HAE cultures. Such mutations should reduce RSV vaccine production costs.

figure zjv0031613410005
Vero cell-derived wild-type and modified RSV (G-L208A) infections of HAE cell cultures.

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)