Most of the PUUV antibody positive voles detected in this work were also PUUV RNA positive (33 out of 37). Among the four that had too low PUUV viral load to be considered RNA positive, one was an immature male.

PUUV antibodies were likely to result from maternal transfer [e.g. [56, 58]]. The three other voles were adults, Gefitinib cost and were probably not shedding PUUV at this time. We could however not investigate the reasons underlying these differences in PUUV viral load between PUUV antibody positive adult voles. We used two appropriate methods to detect negative and positive interactions [43]. We reported significant positive associations between two helminth species (H. mixtum and A. muris-sylvatici) and PUUV infection in bank voles. Because helminths generally drive strong type 2 responses [59], which are antagonistic to type 1 responses involved in the immune defense against hantaviruses [review in [60]], we addressed the question of whether these helminth infections could influence vole susceptibility to PUUV. First, we found that PUUV infection was more often observed in voles coinfected

with H. mixtum, and that PUUV viral loads were slightly higher in voles coinfected with this nematode. These results can be interpreted with regard to the immune knowledge acquired from the close parasite Nippostrongylus (syn. Heligmosomum) brasiliensis, which is extensively used as a laboratory model to study Th2 immunity. In mice and rats, N. brasiliensis induces polarized Th2 responses characterized by elevation Repotrectinib of IgE and Th2 cytokines such as IL-4, IL-5, and IL-13 [e.g. [61, 62]]. This immune response might increase the susceptibility to PUUV. Clomifene On another hand, Reece et al. [62] also reported that the baseline transcription levels of Th1 cytokines (IFN-γ, IL-12, and IL-6) are also elevated in N. brasiliensis-infected mice. This could eFT508 manufacturer explain that the Th2 response induced by

H. mixtum is not strong enough to induce a dramatic increase of PUUV viral loads in coinfected voles. A similar observation had been made by Liesenfeld et al. [45] and Erb et al. [63] on a different biological system. They respectively showed that the densities of Toxoplasma gondii and Mycobacterium bovis in mice were only slightly affected by the presence of N. brasiliensis. Lastly, an added complexity in the interpretation of this coinfection is the possibility that it might be generated by correlated exposure, by parasite longevity and host age, or by differences in the genetic constitution of individual hosts. We can hypothesize that genetic factors of susceptibility might mediate the significant co-occurrence of PUUV and H. mixtum infection. Major histocompatibility complex (Mhc) class II genes could be relevant candidates as their polymorphism seems to influence the risk of PUUV or H. mixtum infection in bank voles [52, 64, 65].