Articles of Significant Interest in This Issue

doi:10.1128/JVI.01915-19

DOI: 10.1128/JVI.01915-19

Barcoded Viruses Reveal Dynamic Dissemination

Enteric viruses infect by the oral route but can disseminate around the body. McCune et al. (e01590-19) used a panel of “barcoded” coxsackieviruses to follow viral population movement in orally infected mice. A broad population of viruses was detectable in a variety of tissues within the first day postinfection and in pancreas and liver as early as 20 minutes postinfection, but very few viruses were present at later time points. These results suggest dynamic spread and restriction of enteric viruses.

Barcoded population of coxsackieviruses in colon tissue after oral inoculation.

Flow Virometry Reveals New Information about Murine Leukemia Virus

Murine leukemia virus (MLV) has been studied for more than half a century, but important questions remain regarding viral RNA genome packaging efficiency and the infectivity of the virus. Renner et al. (e01600-19) utilized flow virometry to determine high-throughput intact viral particle counts and to measure the expression levels of markers on the surface of the virus. Results showed that MLV has an RNA packaging efficiency of about 20% and that only 0.4% of intact viruses are infectious. These findings highlight the potential benefits of innovative flow virometry techniques for analyzing viral particles.

Flow virometry analysis of MLV.

The Essential Importance of Unessential Proteins

During genome biosynthesis of the bacteriophage øX174, parental plus strands are displaced into procapsids as daughter plus strands are synthesized. Thus, single-stranded DNA (ssDNA) genomes are organized and folded into icosahedral symmetry as packaging occurs. Roznowski et al. (e01593-19) found that lethal packaging defects can be rescued by elevating the activity of the highly conserved yet unessential A* protein, an N-terminally truncated version of rolling-circle DNA replication protein A. Similar A/A^* protein pairs occur in other ssDNA viral systems, suggesting common evolutionary mechanisms to ensure the product fidelity of ssDNA packaging reactions.

DNA binding proteins (magenta and purple) and ordered ssDNA density (blue) in the øX174 capsomere.

The Caenorhabditis elegans RIG-I Homolog DRH-1 Mediates an Intracellular Pathogen Response

Detection of pathogen infection by Caenorhabditis elegans remains poorly understood. Sowa et al. (e01173-19) found that the C. elegans retinoic acid-inducible gene I (RIG-I) homolog DRH-1 mediates induction of a novel transcriptional defense program, the intracellular pathogen response (IPR), in response to infection by a natural viral pathogen. These findings suggest an unexpected similarity in the antiviral signaling pathways of C. elegans and mammals, as both detect RNA virus infections via RIG-I-like-receptor recognition of viral replication products to trigger a transcriptional immune response. These results shed light on the regulation of a novel response for pathogen resistance.

Model of DRH-1-mediated intracellular pathogen response (IPR) activation by Orsay virus.

Codon Pair Optimization of Human Respiratory Syncytial Virus

Le Nouën et al. (e01296-19) subjected various open reading frames (ORFs) of human respiratory syncytial virus (RSV) to codon pair optimization (CPO), which increases the amount of codon pairs that are overrepresented in the human genome. CPO of ORFs encoding polymerase complex proteins increased viral gene expression, while CPO of ORFs encoding envelope glycoproteins decreased expression. Unexpectedly, all codon pair-optimized RSVs exhibited marginally reduced replication in rodents and significantly lower levels of serum RSV-neutralizing antibodies. This suggests that the natural codon pair usage of RSV is optimal for viral replication and that CPO can have paradoxical effects on virus replication and the adaptive humoral immune response.