Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis.

Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection. We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load. Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections

Guinea pigs experimentally infected with vaccinia virus replicate and shed, but do not transmit the virus Cobaias infectadas experimentalmente com vírus vaccínia replicam e excretam, porém não transmitem o vírus

The origin of vaccinia viruses (VACV) associated with vesicular disease in cattle and humans in Southeast Brazil remains uncertain, yet the role of wild species in virus transmission has been suggested. This study investigated the susceptibility and transmission potential by guinea pigs (Cavia porcellus) - phylogenetically close to an abundant Brazilian rodent (Cavia aperea) - to two VACV strains (P1V and P2V) isolated from an outbreak of cutaneous disease in horses in Southern Brazil. Eight guinea pigs inoculated intranasally with P1V and P2V (10(6) TCID50.ml-1) did not develop clinical signs, but six animals shed virus in nasal secretions (day 1 to 9 post-inoculation - pi), developed viremia (between days 1 and 10 pi) and seroconverted to VACV. In spite of virus replication and shedding, the virus was not transmitted to sentinel animals by direct or indirect contact (aerosols) or through food and water contaminated with virus. These results demonstrate that, in spite of replicating and shedding the virus, guinea pigs do not transmit the virus upon experimental inoculation. This finding makes unlikely a possible participation of related species in VACV maintenance and transmission in nature.<br>A origem dos vírus vaccínia (VACV), envolvidos em surtos de doença vesicular em bovinos e humanos no Sudeste do Brasil, permanece desconhecida, e a participação de espécies silvestres na manutenção e transmissão do vírus tem sido sugerida. O objetivo deste trabalho foi investigar a susceptibilidade e o potencial de transmissão por cobaias (Cavia porcellus) - filogeneticamente relacionada a uma espécie de roedor, conhecido por preá (Cavia aperea), bastante abundante no país - a duas cepas de VACV (P1V e P2V) isoladas de um surto de doença cutânea em equinos no Rio Grande do Sul. Oito cobaias inoculadas pela via intranasal com uma mistura das amostras P1V e P2V (10(6) DICC50.ml-1) não apresentaram sinais clínicos, porém seis animais excretaram o vírus nas secreções nasais (1 a 9 dias pós-inoculação - pi), desenvolveram viremia (1 a 10 dias pi) e soroconverteram ao VACV. Apesar da replicação e excreção viral, o vírus não foi transmitido a sentinelas por contato direto, indireto (aerossóis) ou por água e alimentos contaminados com fezes deliberadamente contaminadas com o vírus. Esses resultados demonstram que, apesar de replicar e excretar o vírus, as cobaias não transmitem o VACV nas condições estudadas. Esses achados tornam pouco provável a participação de espécies relacionadas na manutenção e transmissão do VACV na natureza