Articles of Significant Interest Selected from This Issue by the Editors

doi:10.1128/JVI.00464-17

DOI: 10.1128/JVI.00464-17

An Archaeal Fusellovirus Does Not Require Nearly Half of Its Genes

Functions of the vast majority of archaeal virus genes are unknown, particularly for viruses from extreme environments. Iverson et al. (e02406-16) engineered site-specific and random mutations in all genes in Sulfolobus spindle-shaped virus 1 (SSV1), the prototypical archaeal fusellovirus. Surprisingly, 17 of 35 genes could be disrupted without abrogating virus infectivity, including that encoding a minor capsid protein, VP3. Viruses lacking the vp3 gene have altered virion morphology. These results provide insights into virus assembly and stability in volcanic hot springs at 80°C and pH 3 and allow focused research on minimal SSV genomes.

Overview of mutations in SSV1 genome.

Host Metabolic Pathways Are Required for Distinct Stages of Kaposi's Sarcoma-Associated Herpesvirus Replication

Viruses rely on host cell metabolism for replication, but the stages of replication at which specific metabolic pathways are required is largely unknown. Sanchez et al. (e02237-16) examined the necessity of host metabolic pathways during lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Glycolysis, glutaminolysis, and fatty acid synthesis (FAS) are required for efficient KSHV replication. Glycolysis is necessary for early gene transcription, while glutaminolysis is necessary for early gene translation but not transcription. Inhibition of FAS does not block viral gene expression but does render intracellular virions noninfectious, indicating that FAS is required for proper virion assembly or maturation.

Steps of KSHV replication for which specific metabolic pathways are required.

Interferon Gamma Inhibits Human Papillomavirus 16 Infection

Human papillomavirus 16 (HPV16) is the prototypical oncogenic HPV, causing multiple human cancers, most notably cervical cancer. Day et al. (e00168-17) discovered that interferon gamma (IFN-γ), an antiviral cytokine, prevents infection by HPV16 and multiple other HPV types. IFN-γ blocks HPV cell entry, resulting in endosomal retention of both the viral genome and the minor capsid protein L2, thereby restricting transmission of the viral genome to the nucleus. By using L1 and L2 chimeric viruses, sensitivity to inhibition by IFN-γ treatment across HPV types was mapped to the L2 protein, shedding new light on HPV-host interactions.

Retention of the viral DNA (green) and minor capsid protein (red) in the endosomes within an IFN-γ-treated cell.

Human Respiratory Syncytial Virus Antibodies Are Diverse and Effective

The antibody response against the respiratory syncytial virus (RSV) G protein is not well understood. Cortjens et al. (e02357-16) found that the frequency of human RSV-specific memory B cells is 1 in 280 in adults, and of these cells, 59% are IgA positive. Monoclonal antibodies (MAbs) were directed against four different epitopes. The MAbs neutralized infection of HEp-2 cells efficiently in the presence of complement, but interestingly, they also neutralized RSV infection of primary human airway epithelial (HAE) cells without complement. This mechanism depended on the epitope specificity of the MAb. Highly specific antibodies could serve as therapeutics and guide vaccine research.