Bell's palsy and lip HSV-1 infection: importance of subcutaneous access.

Although HSV-1 has been implicated in facial palsy for a long time, testing and treating for HSV is not routine. The lack of a meaningful demonstration of how HSV-1 would cause facial palsy has limited progress in this field. Herein we demonstrate that the depth of the lip HSV-1 infection defines the course of the disease, with deeper subcutaneous infection allowing virus access to the facial nerve and causing facial palsy. HSV-1 inoculated subcutaneously caused extensive facial paralysis in cotton rats Sigmodon hispidus, while virus inoculated in the same area of the lip by skin surface abrasion did not. Demyelination along the facial nerve (CN VII) accompanied subcutaneous HSV-1 infection and was identified as the possible underlying mechanism of the disease. This causality demonstration is particularly important in light of increased facial palsy outbreaks associated with SARS-CoV-2 infection and SARS-CoV-2 and influenza vaccinations.

Modeling Human Respiratory Viral Infections in the Cotton Rat (Sigmodon hispidus).

For over three decades, cotton rats have been a preferred model for human Respiratory Syncytial Virus (RSV) infection and pathogenesis, and a reliable model for an impressive list of human respiratory pathogens including adenoviruses, para influenza virus, measles, and human metapneumo virus. The most significant contribution of the cotton rat to biomedical research has been the development of anti-RSV antibodies for prophylactic use in high-risk infants. More recently, however, the cotton rat model has been further explored as a model for infection with other respiratory viral pathogens including influenza and rhinovirus.Together with RSV, these viruses inflict the greatest impact on the human respiratory health.This review will focus on the characteristics of these new models and their potential contribution to the development of new therapies.

Novel drugs targeting Toll-like receptors for antiviral therapy.

Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.