# A lethal juvenile mouse model for the evaluation of antiviral reagents against coxsackievirus A4 **Authors:** Qin Su, Xiao Chen, Zhihui Zheng, Hailin Wei, Jiaxue Zhou, Libing Zhang, Ali Muhammad, Yin Wang, Xiang Chen, Pinghu Zhang PMC · DOI: 10.1016/j.isci.2025.113022 · 2025-06-30 ## TL;DR Researchers created a mouse model to study and test treatments for a virus called coxsackievirus A4, which causes severe illness in children. ## Contribution A lethal juvenile mouse model was developed for evaluating antiviral treatments against coxsackievirus A4. ## Key findings - The YZ08 virus strain was highly lethal to 13-day-old juvenile mice. - The mouse model effectively evaluated the therapeutic efficacy of various antiviral reagents. - Tested reagents prolonged survival, promoted survival rates, and prevented weight loss in infected mice. ## Abstract Coxsackievirus A4 (CVA4) as a pathogen causing severe herpangina has become global outbreak epidemics during the past 5 years. However, there is currently no effective vaccines and drugs available. Here, one mouse-adapted CVA4 virus (YZ08) was cultivated by repeatedly cross-passaging between human RD cells and 11-day-old juvenile mice. Our results revealed the YZ08 virus was highly lethal to 13-day-old juvenile mice. Virus titer assay indicated that the YZ08 virus effectively replicated in juvenile mice. This model was successfully used to evaluate the therapeutic efficacy of herb medicine, anti-CVA4 rabbit sera, and antiviral drugs. Our results indicated that all tested reagents effectively provided protection for CVA4 virus infection by prolonging survival time, promoting survival, and preventing weight loss. Collectively, we successfully established a juvenile mouse model of CVA4 virus, which was a powerful tool for investigating the pathogenesis of CVA4 or evaluating the efficacy of antiviral reagents or vaccines. •One mouse-adapted coxsackievirus A4 (CVA4) strain was cultivated•A 11-day-old juvenile mouse CVA4 infection model has been successfully established•This CVA4 mouse model was successfully used to evaluate the efficacy of antiviral reagents One mouse-adapted coxsackievirus A4 (CVA4) strain was cultivated A 11-day-old juvenile mouse CVA4 infection model has been successfully established This CVA4 mouse model was successfully used to evaluate the efficacy of antiviral reagents Pharmacology; Microbiology; Virology ## Linked entities - **Diseases:** herpangina (MONDO:0005791) - **Species:** Mus musculus (taxon 10090) ## Full-text entities - **Genes:** Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Cxcl10 (C-X-C motif chemokine ligand 10) [NCBI Gene 15945] {aka C7, CRG-2, INP10, IP-10, IP10, Ifi10}, Ccl4 (C-C motif chemokine ligand 4) [NCBI Gene 20303] {aka AT744.1, Act-2, MIP-1B, Mip1b, Scya4}, Cxcl2 (C-X-C motif chemokine ligand 2) [NCBI Gene 20310] {aka CINC-2a, GROb, Gro2, MIP-2, MIP-2a, Mgsa-b}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Il13 (interleukin 13) [NCBI Gene 16163] {aka Il-13}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Ccl11 (C-C motif chemokine ligand 11) [NCBI Gene 20292] {aka Scya11, eotaxin}, Ccl7 (C-C motif chemokine ligand 7) [NCBI Gene 20306] {aka MCP-3, Scya7, fic, marc, mcp3}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Ccl3 (C-C motif chemokine ligand 3) [NCBI Gene 20302] {aka G0S19-1, LD78alpha, MIP-1alpha, MIP1-(a), MIP1-alpha, Mip1a}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Il9 (interleukin 9) [NCBI Gene 16198] {aka Il-9, P40}, Il22 (interleukin 22) [NCBI Gene 50929] {aka IL-22, IL-22a, ILTIFa, If2b1, Iltif}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228} - **Diseases:** lung lesions (MESH:D008171), CVA4 (MESH:D003384), meningitis (MESH:D008580), polio (MESH:D011051), enterovirus infection (MESH:D004769), RD (MESH:D012208), quadriplegia (MESH:D011782), pneumonia (MESH:D011014), pain (MESH:D010146), viral infectious diseases (MESH:D018792), ataxic (MESH:D001039), death (MESH:D003643), HFMD (MESH:D006232), weight loss (MESH:D015431), lethargy (MESH:D053609), viral diseases (MESH:D014777), herpangina (MESH:D006557), necrosis (MESH:D009336), RD (MESH:D000077733), neurological (MESH:D009461), inflammatory (MESH:D007249), pathological (MESH:D005598), CVA6 infection (MESH:D007239), infectious disease (MESH:D003141), myocarditis (MESH:D009205), paralysis (MESH:D010243) - **Chemicals:** nucleoside (MESH:D009705), ethanol (MESH:D000431), paraffin (MESH:D010232), isopropanol (MESH:D019840), Trizol (MESH:C411644), hematoxylin (MESH:D006416), CVA4 (-), formaldehyde (MESH:D005557), eosin (MESH:D004801), H&E (MESH:D006371), Ribavirin (MESH:D012254), agarose (MESH:D012685), chloroform (MESH:D002725), water (MESH:D014867), polysaccharide (MESH:D011134), isoflurane (MESH:D007530), CO2 (MESH:D002245) - **Species:** Coxsackievirus A16 (no rank) [taxon 31704], Coxsackievirus B3 (no rank) [taxon 12072], Coxsackievirus B5 (no rank) [taxon 12074], Enterovirus A71 (no rank) [taxon 39054], Homo sapiens (human, species) [taxon 9606], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Coxsackievirus A4 (no rank) [taxon 42785], Enterovirus (genus) [taxon 12059], Mus musculus (house mouse, species) [taxon 10090] - **Cell lines:** CVA4 — Homo sapiens (Human), Ataxia telangiectasia syndrome, Finite cell line (CVCL_F083), YZ08 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_JW74), RD — Homo sapiens (Human), Embryonal rhabdomyosarcoma, Cancer cell line (CVCL_JB74), Vero — Chlorocebus sabaeus (Green monkey), Spontaneously immortalized cell line (CVCL_0059) ## Figures 8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12304755/full.md --- Source: https://tomesphere.com/paper/PMC12304755