Extensive CD4 and CD8 T Cell Cross-Reactivity between Alphaherpesviruses

The Alphaherpesvirinae subfamily includes HSV types 1 and 2 and the sequence-divergent pathogen varicella zoster virus (VZV). T cells, controlled by TCR and HLA molecules that tolerate limited epitope amino acid variation, might cross-react between these microbes. We show that memory PBMC expansion with either HSV or VZV enriches for CD4 T cell lines that recognize the other agent at the whole-virus, protein, and peptide levels, consistent with bidirectional cross-reactivity. HSV-specific CD4 T cells recovered from HSV-seronegative persons can be explained, in part, by such VZV cross-reactivity. HSV-1–reactive CD8 T cells also cross-react with VZV-infected cells, full-length VZV proteins, and VZV peptides, as well as kill VZV-infected dermal fibroblasts. Mono- and cross-reactive CD8 T cells use distinct TCRB CDR3 sequences. Cross-reactivity to VZV is reconstituted by cloning and expressing TCRA/TCRB receptors from T cells that are initially isolated using HSV reagents. Overall, we define 13 novel CD4 and CD8 HSV–VZV cross-reactive epitopes and strongly imply additional cross-reactive peptide sets. Viral proteins can harbor both CD4 and CD8 HSV/VZV cross-reactive epitopes. Quantitative estimates of HSV/VZV cross-reactivity for both CD4 and CD8 T cells vary from 10 to 50%. Based on these findings, we hypothesize that host herpesvirus immune history may influence the pathogenesis and clinical outcome of subsequent infections or vaccinations for related pathogens and that cross-reactive epitopes and TCRs may be useful for multi-alphaherpesvirus vaccine design and adoptive cellular therapy

The Cocoon Shocks of Cygnus A: Pressures and Their Implications for the Jets and Lobes

We use 2.0 Msec of Chandra observations to investigate the cocoon shocks of Cygnus A and some implications for its lobes and jet. Measured shock Mach numbers vary in the range 1.18–1.66 around the cocoon. We estimate a total outburst energy of $\simeq 4.7\times {10}^{60}\,\mathrm{erg}$, with an age of $\simeq 2\times {10}^{7}\,\mathrm{years}$. The average postshock pressure is found to be $8.6\pm 0.3\times {10}^{-10}\,\mathrm{erg}\,{\mathrm{cm}}^{-3}$, which agrees with the average pressure of the thin rim of compressed gas between the radio lobes and shocks, as determined from X-ray spectra. However, average rim pressures are found to be lower in the western lobe than in the eastern lobe by sime20%. Pressure estimates for hotspots A and D from synchrotron self-Compton models imply that each jet exerts a ram pressure gsim3 times its static pressure, consistent with the positions of the hotspots moving about on the cocoon shock over time. A steady, one-dimensional flow model is used to estimate jet properties, finding mildly relativistic flow speeds within the allowed parameter range. Models in which the jet carries a negligible flux of rest mass are consistent with the observed properties of the jets and hotspots. This favors the jets being light, implying that the kinetic power and momentum flux are carried primarily by the internal energy of the jet plasma rather than by its rest mass

Novel Hendra Virus Variant Detected by Sentinel Surveillance of Horses in Australia

We identified and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be effective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed flying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral-host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by flying foxes