Equine herpesvirus 1 (EHV-1) is a member of the Alphaherpesvirinae, and its broad tissue tropism suggests that EHV-1 may use multiple receptors to initiate virus entry. EHV-1 entry was thought to occur exclusively through fusion at the plasma membrane, but recently entry via the endocytic/phagocytic pathway was reported for Chinese hamster ovary cells (CHO-K1 cells). Here we show that cellular integrins, and more specifically those recognizing RGD motifs such as ␣V␤5, are important during the early steps of EHV-1 entry via endocytosis in CHO-K1 cells. Moreover, mutational analysis revealed that an RSD motif in the EHV-1 envelope glycoprotein D (gD) is critical for entry via endocytosis. In addition, we show that EHV-1 enters peripheral blood mononuclear cells predominantly via the endocytic pathway, whereas in equine endothelial cells entry occurs mainly via fusion at the plasma membrane. Taken together, the data in this study provide evidence that EHV-1 entry via endocytosis is triggered by the interaction between cellular integrins and the RSD motif present in gD and, moreover, that EHV-1 uses different cellular entry pathways to infect important target cell populations of its natural host.

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BackgroundEquine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model.Methodology/Principal FndingssiRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection.Conclusions/SignificancesiRNA treatment has potential for both prevention and early treatment of EHV-1 infections.

State-scale and premises-scale gravity models for the spread of highly pathogenic avian influenza (H5N1) in Nigeria and Ghana were used to provide a basis for risk maps for future epidemics and to compare and rank plausible culling and vaccination strategies for control. Maximum likelihood methods were used to fit the models to the 2006–2007 outbreaks. The sensitivity and specificity of the state-scale model-generated probabilities that any given state would be involved in an epidemic were each 57 %. The premises-based model indicated that reactive, countrywide vaccination strategies, in which the order in which flocks are vaccinated was strictly determined by known risk factors for infection, were more effective in reducing the final size of the epidemic and the epidemic impact than vaccinating flocks at random or ring vaccination. The model suggests that an introduction of highly pathogenic avian influenza (H5N1) into Ghana had a high chance (84 %) of causing a major outbreak. That this did not happen was most probably a result of the very swift Ghanaian response to news of the first introductions.