Herpes virus type 1 (HSV-1) is one of the most widespread human pathogens and accounts for more than 90% of cases of herpes simplex encephalitis (HSE) causing severe and permanent neurologic sequelae among surviving patients. We hypothesize such CNS deficits are due to HSV-1 infection of neural progenitor cells (NPCs). In vivo, HSV-1 infection was found to diminish NPC numbers in the subventricular zone. Upon culture of NPCs in conditions that stimulate their differentiation, we found HSV-1 infection of NPCs resulted in the loss of neuronal precursors with no significant change in the percentage of astrocytes or oligodendrocytes. We propose this is due a direct effect of HSV-1 on neuronal survival without alteration of the differentiation process. The neuronal loss was prevented by the addition of microglia or conditioned media from NPC/microglia co-cultures. Using neutralizing antibodies and recombinant cytokines, we identified interleukin-6 (IL-6) as responsible for the protective effect by microglia, likely through its downstream Signal Transducer and Activator of Transcription 3 (STAT3) cascade.

Infectious diseases may lead to ocular complications including uveitis, an ocular inflammatory condition with potentially sight-threatening sequelae, and conjunctivitis, inflammation of the conjunctiva. Emerging infectious pathogens with known ocular findings include Ebola virus, Zika virus, Avian influenza virus, Nipah virus, severe acute respiratory syndrome coronaviruses, and Dengue virus. Re-emerging pathogens with ocular findings include Toxoplasma gondii and Plasmodium species that lead to malaria. The concept of One Health involves a collaborative and interdisciplinary approach to achieve optimal health outcomes by combining human, animal, and environmental health factors. This approach examines the interconnected and often complex human-pathogen-intermediate host interactions in infectious diseases that may also result in ocular disease, including uveitis and conjunctivitis. Through a comprehensive review of the literature, we review the ophthalmic findings of emerging infectious diseases, pathogenesis, and One Health perspectives that provide further insight into the disease state. While eye care providers and vision researchers may often focus on key local aspects of disease process and management, additional perspective on host-pathogen-reservoir life cycles and transmission considerations, including environmental factors, may offer greater insight to improve outcomes for affected individuals and stakeholders.