This report describes the partial characterization of the first cultivable calicivirus isolated from a European rabbit (Oryctolagus cuniculus), named rabbit calicivirus Oryctolagus-1 and abbreviated RaCv Ory-1. RaCv Ory-1 was isolated from juvenile feeder rabbits displaying symptoms of diarrhea. Absence of neutralization by type specific neutralizing antibodies for 40 caliciviruses and phylogenetic sequence comparisons among the caliciviruses of partial ORF1 and complete ORF2 and ORF3 sequences demonstrate that RaCv Ory-1 is a novel member of the marine calicivirus sub-group. Phylogenetic evaluation of the Caliciviridae indicates that analyses using pooled 3D-polymerase and capsid sequences are more statistically robust than identically executed analyses of single gene sequence data. Phylogenetic analysis of pooled 3D-polymerase and capsid a.a. sequences show canine calicivirus isolate 48 (CaCv-48) to be an intermediate species which forms a node approximately equidistant to the feline, marine, and Sapporo-like caliciviruses. RaCV Ory-1 is suggested as a possible cultivable model of rabbit hemorrhagic disease virus. / Graduation date: 1999

The viral family Herpesviridae consists of large double stranded DNA viruses including eight species that infect humans with varying pathology from benign rashes to cancerous cell transformation. From three subfamilies, alpha-, beta- and gammaherpes, the alphaherpes contains the genera iltovirus, mardivirus, varicellovirus and simplex, two of which, the human simplex viruses I and 2 (HSV) induce life-long infections that have appeared to have coevolved with their hosts from the origins of our species. Unique features of the simplex genus are latency, tropism in dorsal root ganglia neurons, extraordinary high GC content ranging from 65 to 77%, and nucleosome formation of their genomes within the host's nucleus without integration. Reviewing the basic molecular and genetic characteristics of herpes simplex will introduced in Chapter 1, followed by the introduction of a newly sequenced, de novo assembled and predicatively annotated herpes simplex virus, Leporid Herpes Virus-4 (LHV4). Isolated from a virulent outbreak in domesticated rabbits, LHV4 has the smallest reported simplex virus to date at roughly 125,600 base pairs and presents similar pathology seen in rabbit models infected with HSV. Comparative genomics revealed a high degree of sequence similarity and genome synteny between LHV4 and other simplex viruses. Four genes were not computationally predicted in our annotation and may be absent in the LHV4 genome. The absent proteins correspond to: UL56, ICP34.5, US5 and US12 and have postulated roles in membrane trafficking, neurovirulence, apoptotic control and MHC I presentation respectively. The solved genome structure leads to how this compacted genome functions with the noted absences to produce a similar pathology in rabbits to that of HSV and whether other biological correlates will continue to be found in in vitro and in vivo infection. The inverted repeat regions (IR), duplicated and inverted to simplex virus' two larger blocks of protein-coding regions are described in Chapter 3. The similarities and differences in critical genes from the IR that balance latency and replicative viral cycles are compared. A two-fold reduction in IR content indicates the ability for a simplex virus to maintain infectivity despite this large truncation. The appendix describes the eukaryotic phylogeny of two initiating proteins of the mismatch repair (MMR) pathway. MMR proteins are present in the replicative foci of productive herpes virus infection and this analysis may indicate adaptive pressures involved in both genomic fidelity and host tropism. The emerging era of state-of-the-art genome sequencing and computational power advances this newly characterized herpes virus, along with its model host organism, as excellent candidates for systems interaction, and experimental biology. / Graduation date: 2012