bAutophagy is an important innate safeguard mechanism for protecting an organism against invasion by pathogens. We have previously discovered that Kaposi's sarcoma-associated herpesvirus (KSHV) evades this host defense through tight suppression of autophagy by targeting multiple steps of autophagy signal transduction. Here, we report that KSHV K7 protein interacts with Rubicon autophagy protein and inhibits the autophagosome maturation step by blocking Vps34 enzymatic activity, further highlighting how KSHV deregulates autophagy-mediated host immunity for its life cycle.

Kaposi's sarcoma-associated herpesvirus (KSHV) evades host defenses through tight suppression of autophagy by targeting each step of its signal transduction: by viral Bcl-2 (vBcl-2) in vesicle nucleation, by viral FLIP (vFLIP) in vesicle elongation, and by K7 in vesicle maturation. By exploring the roles of KSHV autophagy-modulating genes, we found, surprisingly, that vBcl-2 is essential for KSHV lytic replication, whereas vFLIP and K7 are dispensable. Knocking out vBcl-2 from the KSHV genome resulted in decreased lytic gene expression at the mRNA and protein levels, a lower viral DNA copy number, and, consequently, a dramatic reduction in the amount of progeny infectious viruses, as also described in the accompanying article (A. Gelgor, I. Kalt, S. Bergson, K. F. Brulois, J. U. Jung, and R. Sarid, J Virol 89:5298 -5307, 2015). More importantly, the antiapoptotic and antiautophagic functions of vBcl-2 were not required for KSHV lytic replication. Using a comprehensive mutagenesis analysis, we identified that glutamic acid 14 (E 14 ) of vBcl-2 is critical for KSHV lytic replication. Mutating E 14 to alanine totally blocked KSHV lytic replication but showed little or no effect on the antiapoptotic and antiautophagic functions of vBcl-2. Our study indicates that vBcl-2 harbors at least three important and genetically separable functions to modulate both cellular signaling and the virus life cycle. IMPORTANCEThe present study shows for the first time that vBcl-2 is essential for KSHV lytic replication. Removal of the vBcl-2 gene results in a lower level of KSHV lytic gene expression, impaired viral DNA replication, and consequently, a dramatic reduction in the level of progeny production. More importantly, the role of vBcl-2 in KSHV lytic replication is genetically separated from its antiapoptotic and antiautophagic functions, suggesting that the KSHV Bcl-2 carries a novel function in viral lytic replication. K aposi's sarcoma-associated herpesvirus (KSHV; also referred to as human herpesvirus 8 [HHV-8]) belongs to the gammaherpesvirus family, which includes Epstein-Barr virus (EBV), herpesvirus saimiri (HSV), and murine gammaherpesvirus 68 (MHV-68) (1). KSHV infection is associated with Kaposi's sarcoma (KS), the most common cancer in HIV-infected patients (1). KSHV is also linked to the development of several other lymphoproliferative malignancies, including primary effusion lymphoma (PEL) and a subset of multicentric Castleman's disease (2). Similar to other herpesviruses, the life cycle of KSHV consists of latent and lytic replication phases (3). Following acute infection, KSHV establishes latency in the immunocompetent hosts, where KSHV maintains its genome as an episome and expresses only a limited number of viral proteins or viral mRNAs. Thus, KSHV latency is an effective strategy for evading host immune detection (3). In KS lesions, most of the tumor cells are latently infected by KSHV, indicating that viral latency and latent products are likely essential for the development of KS tumors (3, 4). In ...

The hemagglutination inhibition test was used to determine the prevalence of Newcastle disease virus antibodies in healthy wild song birds (Passeriformes) (N=263), pigeons and doves (Columbifonnes) (n=l35) from Chancay province, Peru. All the animals tested were negative, suggesting that the birds were either not exposed to the virus or that prevalence is below 0.75 %.

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