Abstract
Henipaviruses are emerging zoonotic viruses and causative agents of encephalitis in humans. However, the mechanisms of entry into the central nervous system (CNS) in humans are not known. Here, we evaluated the possible role of olfactory epithelium in virus entry into the CNS. We characterized Hendra virus (HeV) and Nipah virus (NiV) infection of primary human olfactory epithelial cultures. We show that henipaviruses can infect mature olfactory sensory neurons. Henipaviruses replicated efficiently, resulting in cytopathic effect and limited induction of host responses. These results show that human olfactory epithelium is susceptible to infection with henipaviruses, suggesting that this could be a pathway for neuroinvasion in humans. IMPORTANCE Henipaviruses are emerging zoonotic pathogens that can cause acute and severe respiratory and neurological disease in humans. The pathways by which henipaviruses enter the central nervous system (CNS) in humans are still unknown. The observation that human olfactory neurons are highly susceptible to infection with henipaviruses demonstrates that the olfactory epithelium can serve as a site of Henipavirus entry into the CNS.
Highlights
Henipaviruses are emerging zoonotic viruses and causative agents of encephalitis in humans
In order to investigate whether henipaviruses can replicate in human olfactory epithelial cells, hOE cultures were infected with Hendra virus (HeV), Nipah virus (NiV) strain Malaysia (NIV-M; human isolate, Malaysia 1998), and NiV strain Bangladesh (NiV-B; human isolate, Bangladesh 2004), at high and low multiplicities of infection (MOIs) of 1 and 0.01, respectively. hOE were derived from healthy, adult subjects, as previously described [14, 15]
To determine whether olfactory neurons were susceptible to infection with HeV, NiV-B and NiV-M, immunofluorescence staining of viral antigen and olfactory marker protein (OMP; a marker for mature olfactory sensory neurons [OSNs]) was performed in Henipavirus-infected hOE
Summary
Henipaviruses are emerging zoonotic viruses and causative agents of encephalitis in humans. The observation that human olfactory neurons are highly susceptible to infection with henipaviruses demonstrates that the olfactory epithelium can serve as a site of Henipavirus entry into the CNS. We determined the ability of henipaviruses to infect primary cultures of human olfactory epithelial cells and characterize the host response.
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