Study points to active skin-cell role in rabies infection: full analysis
A newly published rabies study is pushing the field to look more closely at the skin, not just the nerve. In work published online April 16, 2026, in the Journal of Investigative Dermatology, investigators reported that human epidermal keratinocytes can be infected by rabies virus, support viral replication, activate antiviral signaling, and pass virus to neuronal cells in a coculture system. The finding helps explain how superficial bites, scratches, or saliva exposure to damaged skin might sometimes lead to neuroinvasion, even when exposure seems limited. (sciencedirect.com)
The study didn’t emerge in a vacuum. In 2025, a related npj Viruses paper from overlapping researchers documented rabies-positive keratinocytes in the epidermis of experimentally infected mice and in skin biopsies from naturally infected dogs with suspected bite or scratch sites. That work was important because it showed keratinocyte infection can occur in vivo in both an experimental model and a natural host. But it also left open a major question: are keratinocytes an early stepping stone into the nervous system, or a late consequence of centrifugal spread after the virus is already established? The authors leaned toward the latter explanation in that earlier paper, because infected keratinocytes were only seen in animals that had already developed disease and weren’t found at preclinical time points. (nature.com)
The new paper moves the mechanism forward by shifting into human skin cell systems. According to the article and the accompanying Elsevier release, both HaCaT cells and primary human epidermal keratinocytes were susceptible to rabies infection in vitro. Infection rates were higher with the silver-haired bat rabies virus strain and the attenuated SAD P5/88 Potsdam strain than with a dog-related strain. The infected keratinocytes also showed measurable immune activation, including changes in surface markers and cytokine release, which suggests they may function as active immune participants at the exposure site rather than simply as tissue the virus passes through. (sciencedirect.com)
One of the most consequential details is the coculture experiment. The team used keratinocytes and neuronal cells separated by a microporous membrane and still observed transfer of virus to the neurons while barrier integrity remained intact, measured with transepithelial electrical resistance. That doesn’t prove the same sequence happens in a live patient or animal immediately after exposure, but it does provide a plausible route for skin-level amplification and handoff to nearby nerves. It also fits with prior observations that intra-epidermal nerve endings are in intimate contact with keratinocytes. (sciencedirect.com)
Expert commentary available through the release was measured rather than sweeping. Corine H. Geurts van Kessel of Erasmus Medical Center said the work raises new questions about how keratinocyte-driven immune responses shape disease progression in rabies and other viral skin infections. That cautious framing matters, because the earlier in vivo paper also found that superficial inoculation of intact, brushed, or superficially scratched skin in mice did not produce rabies, underscoring that biologic plausibility is not the same as proof that every superficial exposure leads to productive infection. (eurekalert.org)
Why it matters: For veterinarians, this is mainly a pathogenesis story with practical implications for risk communication. It reinforces why superficial exposures should still trigger careful rabies assessment, especially when bats are involved or when saliva may have contacted broken skin. It may also help clinicians explain to pet parents, staff members, and exposed colleagues why public health guidance doesn’t rely only on wound depth. For shelter medicine, emergency practice, mixed animal teams, and public health veterinarians, the study supports a more nuanced message: “minor” doesn’t always mean “no risk,” and uncertainty at the skin-nerve interface is one reason exposure protocols remain conservative. (sciencedirect.com)
There are also research implications. The strain-dependent differences seen in keratinocyte infection and immune activation could matter for comparative pathogenesis, particularly when thinking about bat-associated versus dog-associated rabies viruses. And because the 2025 animal work could not reproduce keratinocyte infection in ex vivo skin and did not show disease after superficial skin inoculation, the field still needs in vivo time-course studies that capture the earliest hours and days after exposure. Those studies will be key to determining whether keratinocytes are true early amplifiers, occasional participants, or mostly markers of established infection. (sciencedirect.com)
What to watch: Watch for follow-up animal and translational studies that test early post-exposure skin events in vivo, compare strain behavior more directly, and evaluate whether these findings should influence rabies exposure triage, wound management guidance, or future preventive therapeutics. (sciencedirect.com)