Herpesviruses are prevalent throughout the animal kingdom, and they have coexisted and coevolved along with their host species for millions of years. Herpesviruses carry a large (120-230 kb) double-stranded DNA genome surrounded by a protein capsid, a tegument layer consisting of viral and host proteins, and a lipid bilayer envelope with surface glycoproteins. A key characteristic of these viruses is their ability to enter a latent state following primary infection, allowing them to evade the host’s immune system and persist permanently. Herpesviruses can reactivate from their dormant state, usually during times of stress or when the host’s immune responses are impaired. While herpesviruses can cause complications with severe disease in immune-compromised people, most of the population experiences few ill effects from herpesvirus infections. Indeed, herpes simplex virus 1 (HSV-1) in particular has several features that make it an attractive tool for therapeutic gene delivery. Herpes simplex virus 1 targets and infects specific cell types, such as epithelial cells and neurons. The HSV-1 genome can also accommodate large insertions of up to 14 kb. The HSV-1-based vectors have already achieved success for the oncolytic treatment of melanoma. In addition to serving as a vehicle for therapeutic gene delivery and targeted cell lysis, comparative genomics of herpesviruses HSV-1 and 2 has revealed valuable information about the evolutionary history of both viruses and their hosts. This review focuses on the adaptability of HSV-1 as an instrument for gene delivery and an evolutionary marker. Overall, HSV-1 shows great promise as a tool for treating human disease and studying human migration patterns, disease outbreaks, and evolution.

No abstract

No abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect that occurs in up to 63% of patients and has no known effective treatment. A majority of studies do not effectively assess sex differences in the onset and persistence of CIPN. Here we investigated the onset of CIPN, a point of therapeutic intervention where we may limit, or even prevent the development of CIPN. We hypothesized that cap-dependent translation mechanisms are important in early CIPN development and the bi-directional crosstalk between immune cells and nociceptors plays a complementary role to CIPN establishment and sex differences observed. In this study, we used wild type and eIF4E-mutant mice of both sexes to investigate the role of cap-dependent translation and the contribution of immune cells and nociceptors in the periphery and glia in the spinal cord during paclitaxel-induced peripheral neuropathy. We found that systemically administered paclitaxel induces pain-like behaviors in both sexes, increases helper T-lymphocytes, downregulates cytotoxic T-lymphocytes, and increases mitochondrial dysfunction in dorsal root ganglia neurons; all of which is eIF4E-dependent in both sexes. We identified a robust paclitaxel-induced, eIF4E-dependent increase in spinal astrocyte immunoreactivity in males, but not females. Taken together, our data reveals that cap-dependent translation may be a key pathway that presents relevant therapeutic targets during the early phase of CIPN. By targeting the eIF4E complex, we may reduce or reverse the negative effects associated with chemotherapeutic treatments.

No abstract

No abstract

No abstract