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West Nile virus (WNV), Dengue virus (DEN), Ross River virus (RRV), Venezuelan equine encephalitis virus and chikungunya virus represent significant public health and economic burdens, especially in developing areas where these diseases are most prevalent. There are more than 500 known arboviruses and approximately 100 of them are known to cause human disease. During the past 20 years many factors have converged to cause a dramatic resurgence or emergence of epidemic arboviral diseases affecting both humans and domestic animals. Some of these factors include demographics, social changes, urban sprawl, changes in agricultural practices, genetic changes in pathogens and global climate changes.To successfully develop prophylactic and therapeutic interventions to lessen the toll on human and animal health, key interactions between these viruses, their invertebrate vectors and their vertebrate hosts must be understood. Pathogenic viruses interface with a susceptible host at many points including viral entry, pathogen recognition by the host and engagement of effector molecules of the innate and adaptive immune systems. Glycan components of enveloped viruses have been shown to facilitate many of these pathogen-host interactions, making viral glycan-mediated interactions rational targets for therapeutic intervention. This review will provide a comprehensive overview of glycan-mediated interactions between arboviruses and their mammalian hosts. Key WordsArbovirus ؒ Dendritic cells ؒ Immunity ؒ Glycan ؒ Glycosylation ؒ Lectin ؒ Viral attachment/entry ؒ Virus-host cell interactions Abstract Arthropod-borne viruses (arboviruses) are a significant cause of human and animal disease worldwide. Multiple interactions between virus and the host innate immune system ultimately determine the pathogenesis and clinical outcome of the infection. Evidence is rapidly emerging that suggests viral glycans play a key role in viral pathogenesis by regulating host cell tropism and interactions with the host innate immune response. Glycan-mediated interactions are especially important for arboviruses which must adapt to variable glycosylation systems and cellular receptors within both vertebrate and invertebrate hosts. This review focuses on emerging evidence which supports a crucial role for viral glycans in mediating host cell tropism and regulating the innate antiviral response.

Infection of mice with herpesvirus papio 2 (HVP2) parallels zoonotic monkey B virus infections. A major benefit of the HVP2/mouse model is the existence of two HVP2 subtypes: HVP2nv rapidly invades and destroys the CNS while HVP2ap produces no clinical signs and mild histopathological lesions. However, in the natural baboon host, no difference in pathogenicity of HVP2 subtypes is evident. Primary dermal fibroblast cells were evaluated as a model system for defining virus-host interactions that influence the outcome of a cross-species infection. No differences in plaque formation or virus replication were observed between HVP2 subtypes in primary baboon dermal fibroblast cultures. In contrast, when primary mouse dermal fibroblasts (PMDF) were infected, HVP2nv replicated to higher titers and was more efficient at shutting down host-cell protein synthesis compared to HVP2ap. HVP2ap-infected PMDF cells produced more IFN-beta compared to HVP2nv, and IFN-beta pretreatment of PMDF cultures inhibited HVP2ap replication but did not affect HVP2nv. The differential pathogenicity of HVP2 subtypes in mice and the lack of such differences in the natural baboon host are recapitulated in the primary dermal fibroblast cell culture system. This model may prove useful in examining early, local, host responses that influence the outcome of cross-species infections.

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