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Effective Infection with Dengue Virus in Experimental Neonate and Adult Mice through the Intranasal Route

ABSTRACT: Dengue virus, the causative agent of dengue fever, life-threatening hemorrhagic fever, and shock syndrome, is mainly transmitted to humans through mosquito vectors. It can also be transmitted through atypical routes, including needle stick injury, vertical transmission, blood transfusion, and organ transplantation. In addition, sporadic cases which have no clear infectious causes have raised the respiratory exposure concerns, and the risks remain unclear. Here, we analyze the respiratory infectivity of the dengue virus in BALB/c suckling and adult immunodeficient mice by the intranasal inoculation of dengue virus serotype 2. The infected mice presented with clinical symptoms, including excitement, emaciation, malaise, and death. Viremia was detected for 3 days post inoculation. Histopathological changes were observed in the brain, liver, and spleen. The virus showed evident brain tropism post inoculation and viral loads peaked at 7 days post inoculation. Furthermore, the virus was isolated from the infected mice; the sequence homology between the origin and isolates was 99.99%. Similar results were observed in adult IFN-α/β receptor-deficient mice. Overall, dengue virus can infect suckling mice and adult immune-deficient mice via the nasal route. This study broadens our perception of atypical dengue transmission routes and provides evidence of nasal transmission of dengue virus in the absence of mosquito vectors.

SUBMITTER: Qiu M

PROVIDER: S-EPMC9322762 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Oral transmission of Chagas disease has been documented in Latin American countries. Nevertheless, significant studies on the pathophysiology of this form of infection are largely lacking. The few studies investigating oral route infection disregard that inoculation in the oral cavity (Oral infection, OI) or by gavage (Gastrointestinal infection, GI) represent different infection routes, yet both show clear-cut parasitemia and heart parasitism during the acute infection. Herein, BALB/c mice were subjected to acute OI or GI infection using 5x10(4) culture-derived Trypanosoma cruzi trypomastigotes. OI mice displayed higher parasitemia and mortality rates than their GI counterparts. Heart histopathology showed larger areas of infiltration in the GI mice, whereas liver lesions were more severe in the OI animals, accompanied by higher Alanine Transaminase and Aspartate Transaminase serum contents. A differential cytokine pattern was also observed because OI mice presented higher pro-inflammatory cytokine (IFN-γ, TNF) serum levels than GI animals. Real-time PCR confirmed a higher TNF, IFN-γ, as well as IL-10 expression in the cardiac tissue from the OI group compared with GI. Conversely, TGF-β and IL-17 serum levels were greater in the GI animals. Immunolabeling revealed macrophages as the main tissue source of TNF in infected mice. The high mortality rate observed in the OI mice paralleled the TNF serum rise, with its inhibition by an anti-TNF treatment. Moreover, differences in susceptibility between GI versus OI mice were more clearly related to the host response than to the effect of gastric pH on parasites, since infection in magnesium hydroxide-treated mice showed similar results. Overall, the present study provides conclusive evidence that the initial site of parasite entrance critically affects host immune response and disease outcome. In light of the occurrence of oral Chagas disease outbreaks, our results raise important implications in terms of the current view of the natural disease course and host-parasite relationship.

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Effective Infection with Dengue Virus in Experimental Neonate and Adult Mice through the Intranasal Route

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