PHEV infection: A promising model of betacoronavirus-associated neurological and olfactory dysfunction

PLoS Pathog. 2022 Jun 27;18(6):e1010667. doi: 10.1371/journal.ppat.1010667. eCollection 2022 Jun.

Abstract

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.

MeSH terms

  • Animals
  • Betacoronavirus 1* / physiology
  • COVID-19*
  • Coronavirus Infections / pathology*
  • Humans
  • Mice
  • Olfaction Disorders* / virology
  • SARS-CoV-2
  • Smell
  • Swine

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant numbers 32172805, 32172828, 31902262, and 31872446); the Scientific and Technological Project of Jilin Province (grant numbers 20210202041NC to WH), the Youth Science and Technology Talent Support Project of Jilin Province (grant numbers QT202015 to ZL). The funder had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.