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Latency-associated nuclear antigen 1 (LANA1) binds to Kaposi's sarcoma-associated herpesvirus (KSHV) terminal repeat (TR) DNA to mediate episome replication and persistence. LANA1 concentrates at sites of TR DNA along mitotic chromosomes, consistent with tethering KSHV DNA to chromosomes for efficient segregation of episomes to progeny nuclei. We now investigate LANA1 C-terminus self-association and DNA binding. The TR DNA binding domain was localized to LANA1 residues 996-1139. Scanning deletions within this region ablated both LANA1 oligomerization and DNA binding, consistent with a requirement for oligomerization to bind DNA. Furthermore, LANA1 bound TR DNA as an oligomer. Deletion of amino acids 1007-1021, N-terminal to the LANA1 oligomerization domain, ablated DNA binding, DNA replication, and episome persistence, implicating these residues in contacting DNA. Indeed, LANA1 residues 1007-1021 correspond to EBNA1 residues that contact the cognate sequence. Like EBNA1, the LANA1 DNA-binding domain has oligomerization activity and critical residues essential for recognizing DNA.

This communication describes our ongoing studies of the interaction of the mouse host and vesicular stomatitis virus (VSV). When VSV is applied to the nasal neuroepithelium, it initially replicates in olfactory receptor neurons, and is transmitted along the olfactory nerve to the central nervous system (CNS) within 12 hours. In the olfactory bulb, the virus replicates invasively through the layers of the olfactory bulb, reaching the olfactory ventricle by day 4-5 post infection, and the hindbrain by day 8 post infection. In mice, infection may result in a 50% mortality rate. The crucial host innate and specific immune responses responsible for restricting viral propagation and caudal spread of the virus will be discussed. The efficacy of interleukin-12 (IL-12) treatment for enhanced viral clearance and promotion of host recovery are described along with the implications for treatment of human encephalitis. The hosts' response to infection is also regulated by the sex of the host, and the age at infection. The role of specific mucosal humoral immunity and systemic cellular immunity in prevention of infection are described.