Photo Credit: Sergey Nivens

Previously thought to infect only the respiratory epithelium, research in The Journal of Infectious Diseases shows that RSV can also spread to nerve cells.

Researchers report in The Journal of Infectious Diseases that RSV, previously thought to infect only the respiratory epithelium, also spreads to nerve cells.

“Our cellular physiology project is the first study that shows that RSV, a dangerous infection in older adults, can also infect the peripheral nerves and that the virus can jump from peripheral nerves into spinal neurons,” says senior study author Giovanni Piedimonte, MD. “Our findings suggest that RSV disrupts neuronal function directly by infecting peripheral neurons and indirectly by infecting resident monocytes. Inflammatory chemokines likely mediate both mechanisms. This is very important because around 40% of patients who develop RSV infection have some neurologic symptoms,” he adds.

“Viruses have not been thought able to pass through the blood-brain barrier to enter the central nervous system. However, the peripheral nerves we infected transferred the virus to CNS spinal nerves they were in synaptic contact with,” he explains. “So, peripheral nerves may act as a Trojan horse to allow the virus to enter the CNS.”

Reproducing Three-Dimensional Nerve Cell Architecture

Through the novel process of microphysiological nerve culture, Dr. Piedimonte and his colleagues reproduced the three-dimensional architecture of nerves. They applied a recombinant RSV-A2 strain that expressed the tandem dimer Tomato protein to cultures of embryonic dorsal root ganglia and spinal cord dorsal horn rat cells and to human induced pluripotent stem cell-derived pain receptor cultures.

In these cultured nerve cells, RSV infected neurons, macrophages, and dendritic cells in two different ways based on initial viral load. With low viral load, infection was transient, mainly involved macrophages, and induced moderate chemokine release with transient neural hypersensitivity. Higher viral load led to persistent monocytes and neuronal cell infection and induced robust chemokine release, leading to progressive neurotoxicity.

By contrast, in spinal cord cultures, RSV infected microglia and dendritic cells but not neurons, with moderate chemokine expression. Infection persistence varied, and the virus was detected in dendritic cells up to 30 days post-inoculation.

Building on Previous Research

“The prevailing thought has been that RSV causes infections that are limited to the respiratory system,” Dr. Piedimonte says. “However, several years ago, my colleagues and I showed for the first time that this virus can enter the bloodstream and travel from the respiratory system to bone marrow cells.”

The authors plan to identify the specific mechanisms of action involved in RSV spread to nerve cells and the clinical consequences of nerve invasion.

RSV Vaccinations Offer Protection

Dr. Piedimonte urges clinicians to strongly advise RSV vaccinations to their patients who are elderly.

“The number of elderly people who die of RSV infection may be even higher than those who die of other viruses,” he says. “Last year, for the first time in more than 65 years since the virus was discovered, the FDA approved two vaccines against RSV. We believe that vaccination can prevent long-term respiratory problems and neurologic complications.”

Key Takeaways

• RSV was previously thought to infect only the respiratory epithelium.
• Approximately 40% of patients with RSV have some neurologic symptoms.
• Study results show that RSV can infect the peripheral nerves, jumping from there to spinal neurons.
• Vaccination can prevent long-term respiratory problems and neurologic complications.