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Lentiviruses exhibit a high degree of species specificity. Lee et al. (e02134-16) evaluated transmission, fitness, and adaptation of a lentivirus identified in free-ranging bobcats and mountain lions. Ancestral reconstruction and viral fitness analyses indicate that bobcats are the primary host. Bobcat lentivirus transmitted to mountain lions experienced strong selective pressure. There was high-frequency intraspecific transmission among relic Florida panthers, whereas transmission rarely occurred among California mountain lions. Given the emergence of HIV following simian immunodeficiency virus (SIV) exposure, understanding processes that regulate cross-species lentiviral transmissions opens a unique opportunity to examine events leading to lentiviral emergence.
Epstein-Barr virus (EBV) establishes different mechanisms of latency in B cells, including a highly transforming form (type III) and a more restricted form (type I) in which most viral gene expression is silenced by promoter DNA methylation. Wille et al. (e01987-16) show that TET2, a cellular enzyme that converts 5-methylcytosine into 5-hydroxymethylcytosine, promotes type III latency in EBV-infected B cells by enhancing the capacity of the EBV transcription factor EBNA2 to activate latent EBV promoters. Furthermore, TET2 expression is repressed in germinal center B cells, allowing restricted type I latency in this B cell type. This work points to a critical function for TET2 in EBV latency determination.
Zika virus (ZIKV) is a major public health threat. Understanding its replication mechanisms and the identification of inhibitors targeting viral enzymes essential for replication are of particular interest. Coutard et al. (e02202-16) present structural and functional characterization of the NS5 methyltransferase of ZIKV. The results show that the ZIKV methyltransferase harbors the canonical flavivirus methyltransferase fold embedding N7- and 2′-O-methyltransferase activities. In addition, the structures pinpoint features useful for both a better understanding of viral RNA methylation and rational drug design.
As a member of the Rho GTPase family of enzymes, Cdc42 mediates its functions via interactions with different proteins. Xu et al. (e01916-16) found that when Cdc42 interacts with an arginine kinase (AK) that binds to the white spot syndrome virus (WSSV) envelope protein VP26, it promotes WSSV replication. However, Cdc42 interactions with the active site of AK and resultant suppression of its enzymatic activity inhibit WSSV replication in shrimp. This study identifies a new mechanism by which small GTPases defend against pathogens and enriches the knowledge of innate immunity of invertebrates.
The increasing incidence of dengue virus (DENV) infections has heightened the global public health interest in effective vaccination strategies. It is likely that a successful vaccine will induce immunity similar to anti-dengue responses in natural infection. Angelo et al. (e02147-16) demonstrate that CD4+ T cell responses elicited by the tetravalent dengue vaccine TV005 parallel those induced by natural infection in magnitude, HLA restriction, and antigen specificity. Detailed knowledge of T cell responses elicited by this vaccine contribute to the identification of correlates of protection against DENV.