Evidence map›Paper›PMID 42088519›Full record

ArticleFrontiers in immunology2026

Intranasal VACV VR-1354 infection impairs chemosensory function and induces olfactory bulb neuroinflammation in mice.

Shun Li, Yunxiang Wu, Chao Wang, Hanqing Wu, Lin Yang, Lixiang Chen, Hua Yang, Jun Zhang, Xiaohui Zhou

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Shun Li *Department of Animal Model, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Yunxiang Wu *Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China.
Chao Wang *Department of Animal Model, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Hanqing WuSchool of Life Sciences, Shanghai Normal University, Shanghai, China.
Lin YangSchool of Life Sciences, Shanghai Normal University, Shanghai, China.
Lixiang ChenDepartment of Animal Model, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Hua YangDepartment of Animal Model, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Jun ZhangSchool of Life Sciences, Shanghai Normal University, Shanghai, China.
Xiaohui ZhouDepartment of Animal Model, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vaccinia virus (VACV) and monkeypox virus (MPXV) are closely related members of the family Poxviridae, genus Orthopoxvirus, both capable of causing systemic infections with potential neurological complications. Although live, replication-competent VACV strains were historically used in smallpox vaccination, their clinical use was associated with rare but severe central nervous system (CNS)-related adverse events. Despite this, the mechanisms underlying VACV-induced CNS pathology, particularly olfactory dysfunction, remain poorly characterized. In this study, we found VACV-VR1354, a tissue culture-adapted derivative of the neurovirulent Western Reserve strain, can invade the CNS via the olfactory route and induce olfactory impairment. By using an intranasal infection model in two inbred mouse strains-C57BL/6N and BALB/c, we demonstrate that VACV-VR1354 efficiently disseminates from the nasal mucosa to the brain, as evidenced by a spatiotemporal gradient of viral DNA load (nasal mucosa > olfactory bulb > cerebrum > cerebellum). Evans blue extravasation assays indicated a transient increase in blood-brain barrier (BBB) permeability in the olfactory bulb, peaking at 7 days post-infection (dpi) and resolving by 14 dpi, with more pronounced effects in C57BL/6N mice. Neuroinvasion was accompanied by robust microglial and astrocytic activation, as well as injury to mature olfactory sensory neurons, particularly at 7 dpi. Transcriptomic profiling of the olfactory bulb revealed significant downregulation of olfactory receptor (OR) genes, with the downregulated genes significantly enriched in olfactory transduction pathways. Concurrently, strong upregulation of proinflammatory cytokines, chemokines, and interferon-stimulated genes (ISGs) was detected in the olfactory bulb tissue, indicative of intense neuroinflammation. Behaviorally, infected C57BL/6N mice exhibited impaired aversion to camphor odor between 14 and 49 dpi, with full functional recovery observed by 56 dpi. Collectively, our findings showed that intranasal infection of mice with VACV-VR1354 leads to a transient increase BBB permeability, neuroinflammation, and reversible olfactory/chemosensory impairment. This murine model recapitulates key features of post-viral olfactory loss and establishes a valuable platform for mechanistic studies of orthopoxvirus neuropathogenesis and therapeutic evaluation of interventions targeting viral neuroinvasion and sensory recovery.

Indexed as

Neuroinflammatory DiseasesOlfactory BulbVacciniaVaccinia virusAnimalsBlood-Brain BarrierDisease Models, AnimalFemaleMiceMice, Inbred BALB CMice, Inbred C57BLBlood-brain barrierintranasal infectionneuroinflammationolfactory dysfunctionVACV VR-1354

Identifiers

PMID42088519
PMCPMC13135986

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.