BALB/c mice challenged with SARS-CoV-2 B.1.351 β variant cause pathophysiological and neurological changes within the lungs and brains

J Gen Virol. 2024 Oct;105(10):002039. doi: 10.1099/jgv.0.002039.

Abstract

Up to one-third of individuals suffering from acute SARS-CoV-2 infection with the onset of severe-to-mild diseases could develop several symptoms of neurological disorders, which could last long after resolving the infection, known as neuro-COVID. Effective therapeutic treatments for neuro-COVID remain unavailable, in part, due to the absence of animal models for studying its underlying mechanisms and developing medical countermeasures against it. Here, we explored the impact of SARS-CoV-2 infection on the well-being of respiratory and neurological functions of BALB/c mice by using a clinical isolate of β-variant, i.e. B.1.351. We found that this β-variant of SARS-CoV-2 primarily infected the lungs, causing tissue damage, profound inflammatory responses, altered respiratory functions and transient but significant hypoxia. Although live progeny viruses could not be isolated, viral RNAs were detected across many anatomical regions of the brains in most challenged mice and triggered activation of genes encoding for NF-kB, IL-6, IP-10 and RANTES and microglial cells. We noted that the significantly activated IL-6-encoded gene persisted at 4 weeks after infection. Together, these results suggest that this B.1.351/BALB/c model of SARS-CoV-2 infection warrants further studies to establish it as a desirable model for studies of neuropathogenesis and the development of effective therapeutics of neuro-COVID.

Keywords: B.1.351; BALB/c; SARS-CoV-2; neuro-COVID; neuropathogenesis.

MeSH terms

  • Animals
  • Brain* / pathology
  • Brain* / virology
  • COVID-19* / immunology
  • COVID-19* / virology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Female
  • Humans
  • Lung* / pathology
  • Lung* / virology
  • Mice
  • Mice, Inbred BALB C*
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / physiology

Substances

  • Cytokines

Supplementary concepts

  • SARS-CoV-2 variants