No abstract

Feline morbillivirus (FeMV) is a recently discovered pathogen of domestic cats and has been classified as a morbillivirus in the Paramyxovirus family. We determined the complete sequence of FeMV US5 directly from an FeMV-positive urine sample without virus isolation or cell passage. Sequence analysis of the viral genome revealed potential divergence from characteristics of archetypal morbilliviruses. First, the virus lacks the canonical polybasic furin cleavage signal in the fusion (F) glycoprotein. Second, conserved amino acids in the hemagglutinin (H) glycoprotein used by all other morbilliviruses for binding and/or fusion activation with the cellular receptor CD150 (signaling lymphocyte activation molecule [SLAM]/F1) are absent. We show that, despite this sequence divergence, FeMV H glycoprotein uses feline CD150 as a receptor and cannot use human CD150. We demonstrate that the protease responsible for cleaving the FeMV F glycoprotein is a cathepsin, making FeMV a unique morbillivirus and more similar to the closely related zoonotic Nipah and Hendra viruses. We developed a reverse genetics system for FeMV US5 and generated recombinant viruses expressing Venus fluorescent protein from an additional transcription unit located either between the phospho-protein ( P ) and matrix ( M ) genes or the H and large ( L ) genes of the genome. We used these recombinant FeMVs to establish a natural infection and demonstrate that FeMV causes an acute morbillivirus-like disease in the cat. Virus was shed in the urine and detectable in the kidneys at later time points. This opens the door for long-term studies to address the postulated role of this morbillivirus in the development of chronic kidney disease.

The platinum(II) organoamides [Pt(NRCH2)2L2] (L = pyridine (py), R = p-HC6F4, C6F5,p-IC6F4,p-CIC6F4,p-C6F5C6F4; L = 4-methylpyridine, R = p-HC6F4) and [Pt(NRCH2CH2NR')(py)2] (R = p-HC6F4, R' = C6F5, p-BrC6F4, or p-MeC6F4) inhibit the growth of murine L1210 leukemia cells in culture with ID50 values for continuous exposure in the range 0.6-2.7 microM. Representative complexes are also active against L1210 cells in 2-h pulse exposures, as well as against the cisplatin-resistant variant L1210/DDP and human colonic carcinoma cell lines HT 29 and BE. Three complexes [Pt(NRCH2)2L2] (R = p-HC6F4, C6F5, or p-IC6F4) have good activity (T/C greater than or equal to 180%) against P388 leukemia in mice, and all other compounds tested are active except when R = p-C6F5C6F4, L = py. Although the molecular basis of the biological activity of these complexes is not known, the observation of good activity for amineplatinum(II) compounds with no hydrogen substituents on the nitrogen donor atoms introduces a new factor in the anticancer behavior of platinum(II) complexes.

No abstract

The Epstein-Barr virus (EBV) protein BHRF1 (BamHI rightward reading frame 1) was the first viral member of the Bcl-2 family of apoptosis-regulating proteins described. In vitro studies imply that BHRF1 is dispensable for virus-induced cellular transformation and virus replication. However, in contrast to several essential viral genes that show divergence outwith their functional domains, sequence data from a wide range of EBV isolates show there is striking conservation of the BHRF1 gene. Contrary to the in vitro studies, the high degree of conservation hints at a more important role for BHRF1. Analogous viruses are endemic in each of the higher primate species. Whilst their genome organisation is colinear, limited sequence analysis indicates that the viruses have diverged significantly and that only important functional domains of proteins are likely to be conserved. We have isolated the BHRF1 equivalents from the viruses which infect chimpanzees (Herpesvirus pan) and baboons (Herpesvirus papio) and find that they are highly homologous in both species, strengthening the hypothesis that BHRF1 plays a significant, evolutionarily conserved function in vivo and that changes to the protein are not well tolerated.