Expression of herpes simplex virus 1 MicroRNAs in cell culture models of quiescent and latent infection

To facilitate studies of herpes simplex virus 1 latency, cell culture models of quiescent or latent infection have been developed. Using deep sequencing, we analyzed the expression of viral microRNAs (miRNAs) in two models employing human fibroblasts and one using rat neurons. In all cases, the expression patterns differed from that in productively infected cells, with the rat neuron pattern most closely resembling that found in latently infected human or mouse ganglia in vivo

Maternal immunization confers protection against neonatal herpes simplex mortality and behavioral morbidity

Neonatal herpes simplex virus (nHSV) infections cause devastating morbidity and mortality in infants. Most nHSV cases are associated with primary maternal infection, consistent with the hypothesis that maternal immunity is protective. In humans, we found HSV-specific neutralizing antibodies in newborns of immune mothers, indicating that placentally transferred HSV-specific antibody is protective. Using a murine model, we showed that passive administration of HSV-specific antibody to dams prevented disseminated infection and mortality in pups. Maternal immunization with an HSV-2 replication-defective vaccine candidate, dl5-29, led to transfer of HSV-specific antibodies into neonatal circulation that protected against nHSV neurological disease and death. Furthermore, we observed considerable anxiety-like behavior in adult mice that had been infected with low doses of HSV as neonates, despite a notable lack of signs of infection. This phenotype suggests that nHSV infection can have an unsuspected and permanent impact on behavior. These behavioral sequelae of nHSV were prevented by maternal immunization with dl5-29, demonstrating an unexpected benefit of immunization. These findings also support the general concept that maternal immunization can prevent neurotropic neonatal infections and associated morbidity and mortality.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The right place for me: A moderated mediation model to explain the involvement of employees aged over 50 years

Over the past decades, employment rates of older workers in most Western countries have rapidly increased. Hence, there is a growing interest in identifying the organizational dimensions that might impact the psychosocial adjustment of workers aged over 50 years. This study focuses on perceived organizational support (POS) and identity‐related measures (identification and authenticity) as key organizational components for workers at this stage of life. Furthermore, in the relationships discussed, we explore the moderating role of perceived age discrimination. In an ample sample of older workers (N = 4,563, aged 50–66 years), a moderated mediational model was tested where older workers' involvement was associated to POS. In the model, this relationship was mediated by organizational identification and authenticity, and the association between POS, identity‐related measures, and involvement was moderated by age‐based discrimination. Results showed that POS is associated with organizational involvement via organizational identification and authenticity and that high level of age discrimination decreased the positive association between POS, organizational identification, authenticity, and involvement

Make yourselves scarce: The effect of demographic change on the relative wages and employment rates of experienced workers

This paper studies the impact of demographic change on experienced workers’ relative wages and employment rates. We investigate empirical predictions from aframework of supply and demand for experience skill, using variation across U.S. local labor markets (LLMs) over the last decades and instrumenting experienceskill supply by the LLMs’ age structures a decade earlier. We find that aging substantially reduces experienced workers’ relative wages and full-time employmentrates, and also their labor market participation rates. Our results imply that the effect of demographic change on labor markets might be more severe than previously recognized, as it reaches beyond wages

Linking indirect effects of cytomegalovirus to modulation of monocyte innate immune function

Cytomegalovirus (CMV) is an important cause of morbidity and mortality in the immunocompromised host. In transplant recipients, a variety of clinically important "indirect effects" are attributed to immune modulation by CMV, including increased mortality from fungal disease, allograft dysfunction and rejection in solid organ transplantation, and graft-versus-host-disease in stem cell transplantation. Monocytes, key cellular targets of CMV, are permissive to primary, latent and reactivated CMV infection. Here, pairing unbiased bulk and single cell transcriptomics with functional analyses we demonstrate that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. Simultaneously, CMV-infected monocytes upregulate antiviral, pro-inflammatory chemokine, and inflammasome responses associated with allograft rejection and graft-versus-host disease. Our study demonstrates that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes, explaining in part, its paradoxical "indirect effects" in transplantation. These data could provide innate immune targets for the stratification and treatment of CMV disease.</p