Pathogenicity and transmissibility of Mpox virus in African dormice.

Abstract

The global spread of Mpox virus (MPXV) poses a major public health challenge, yet reliable and consistent animal models for MPXV evaluation remain limited, which hinders progress in developing treatment strategies and transmission-blocking technologies. As natural hosts, African dormice (<i>Graphiurus</i> spp.) are promising candidates, and several studies have partially examined MPXV pathogenicity in dormice. However, the transmission dynamics and viral shedding kinetics of MPXV in dormice remain largely uncharacterized. This study systematically evaluated MPXV pathogenicity and transmissibility in dormice. Experimental results demonstrated that dormice are highly susceptible to MPXV infection. Following intranasal inoculation, MPXV caused significant weight loss, lethal infections, and multi-organ pathological damage, with robust viral replication in respiratory and liver tissues. Notably, MPXV efficiently transmitted among dormice through direct contact, with one-third of contact-exposed dormice shedding infectious viruses and two-thirds exhibiting seropositivity. Additionally, one-third of dormice exposed to airborne particles exhibited seropositivity; however, no infectious viruses were detected in their respiratory tissues. This suggests that the airborne transmissibility of MPXV among dormice is relatively limited. Furthermore, infected dormice continuously released large quantities of virus-laden aerosols, peaking at 12 dpi (3.78 ± 1.01 × 10⁶ copies/dormouse/hour of respiration). Particle size analysis revealed that viral copies in ≥7 µm coarse particles accounted for >90.9% of exhaled viral aerosols during peak shedding (8-14 dpi). These findings indicate that African dormice are a suitable animal model for assessing MPXV infection, pathogenicity, and transmission. Simultaneously, enhanced surveillance of wild dormouse populations is essential given their potential role in MPXV transmission chains.<h4>Importance</h4>The global spread of monkeypox virus (MPXV) clade IIb has highlighted the urgent need for reliable animal models to investigate its biological characteristics. This study established an African dormouse (Graphiurus spp.) model and systematically characterized the pathogenicity and transmissibility of a clade IIb strain (hMPXV/China/GZ8H-01/2023). Intranasal inoculation induced significant weight loss, lethal infections, and multi-organ pathology, with robust viral replication in the respiratory and liver tissues. Direct contact transmission was efficient: 1/3 of contact-exposed dormice shed infectious virus, while 2/3 showed seropositivity. Although airborne exposure resulted in 1/3 seropositivity, no infectious virus was detected, thereby indicating limited airborne transmission. Infected dormice emitted abundant virus-laden aerosols, peaking at 3.78 ± 1.01×10⁶ copies/dormouse/hour at 12 days post-infection (dpi). These findings establish African dormice as effective models for studying MPXV infection, pathogenicity, and transmission. Enhanced surveillance of wild dormouse populations is critical due to their potential role in MPXV transmission chains.