The ability of antisera raised against a candidate Japanese encephalitis virus (JEV) vaccine, ChimeriVax-JE, and the currently licensed vaccine, JE-VAX, to protect against strains of JEV representing the four major genotypes was assessed. Neutralization assays and passive protection studies in mice showed that greatest protection was provided against strains of genotypes II and III, although some protection was also afforded against genotypes I and IV strains. ChimeriVax-JE stimulated protection that was comparable or superior to the JE-VAX control.

ABSTRACT A hamster viscerotropic strain of yellow fever (YF) virus has been derived after serial passage of strain Asibi through hamsters. The parental Asibi/hamster p0 virus causes a mild and transient viremia in hamsters with no outward, clinical signs of illness. In contrast, the viscerotropic Asibi/hamster p7 virus causes a robust viremia, severe illness, and death in subadult hamsters. The genome of the hamster viscerotropic Asibi/hamster p7 virus has been sequenced and compared with the parental nonviscerotropic Asibi/hamster p0 virus identifying 14 nucleotide changes encoding only seven amino acid substitutions. The majority of these substitutions (five of seven) fall within the envelope (E) protein at positions Q27H, D28G, D155A, K323R, and K331R. These results support an important role for the E protein in determining YF virus viscerotropism.

Despite recent advances in the genetics of West Nile (WN) virus, relatively little is known about the molecular basis of virulence of this virus. In particular, although the genotype of the WN virus strain that was recently introduced into North America has been determined, there have been few experimental studies on the virulence phenotype of the virus. We compared genetic and neurovirulence properties of 19 strains of WN virus, including 2 from North America, and observed significant differences in their neuroinvasive phenotype in mice and hamsters that correlated with virus genotype. Virus isolated in North America was found to be highly neuroinvasive with a lack of age-related resistance to infection in mice normally associated with mosquito-borne flaviviruses.

Jatobal (JAT) virus was isolated in 1985 from a carnivore (Nasua nasua) in Tucuruı́, Pará state, Brazil and was classified as a distinct member of the Simbu serogroup of the Bunyavirus genus, family Bunyaviridae on the basis of neutralization tests. On the basis of nucleotide sequencing, we have found that the small (S) RNA of JAT virus is very similar (>95% identity) to that of Oropouche (ORO) virus, in particular, the Peruvian genotype of ORO virus. In comparison, limited nucleotide sequencing of the G2 protein gene, encoded by the middle (M) RNA, of JAT and ORO viruses, revealed relatively little identity (<66%) between these two viruses. Neutralization tests confirmed the lack of cross-reactivity between the viruses. These results suggest that JAT virus is a reassortant containing the S RNA of ORO virus. JAT virus was attenuated in hamsters compared to ORO virus suggesting that the S RNA of ORO virus is not directly involved in hamster virulence.

The 3' non-coding region (3'NCR) of strains of dengue 1 (DEN 1), DEN 2, DEN 3, and DEN 4 viruses, isolated in different geographical regions, was sequenced and compared to published sequences of the four dengue viruses. A total of 50 DEN 2 strains was compared: 7 West African strains, 3 Indonesian mosquito strains, 1 Indonesian macaque isolate, and 39 human isolates from Southeast Asia, the South Pacific, and the Caribbean and Americas. Nucleotide sequence alignment revealed few deletions and no repeat sequences in the 3' NCR of DEN 2 viruses and showed that much of the 3' NCR was well conserved. The strains could be divided into two groups, sylvatic and human/mosquito/macaque, based on nucleotide sequence homology. A hypervariable region was identified immediately following the NS5 stop codon, which involved a 2-10 nucleotide deletion in human, mosquito, and macaque isolates compared with the sylvatic strains. The DEN 2 3'NCR was also compared with 3'NCR sequences from strains of DEN 1, DEN 3, and DEN 4 viruses. DEN 1 was found to have four copies of an eight nucleotide imperfect repeat following the NS5 stop codon, while DEN 4 virus had a deletion of 75 nucleotides in the 3'NCR. We propose that the variation in nucleotide sequence in the 3'NCR may have evolved as a function of DEN virus transmission and replication in different mosquito and non-human primate/human host cycles. The results from this study are consistent with the hypothesis that DEN viruses arose from sylvatic progenitors and evolved into human epidemic strains. However, the data do not support the hypothesis that variation in the 3'NCR correlates with DEN virus pathogenesis.

Annals of the New York Academy of SciencesVolume 951, Issue 1 p. 332-335 West Nile Virus Strains Differ in Mouse Neurovirulence and Binding to Mouse or Human Brain Membrane Receptor Preparations DAVID W. C. BEASLEY, Corresponding Author DAVID W. C. BEASLEY WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USAAddress for correspondence: David W. C. Beasley, Department of Pathology, University of Texas Medical Branch, Galveston, TX 777555-0609. Voice: 409-772- 2547; fax: 409-747-2415; dwbeasle@utmb.edu.Search for more papers by this authorLI LI, LI LI WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USASearch for more papers by this authorMIGUEL T. SUDERMAN, MIGUEL T. SUDERMAN WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USASearch for more papers by this authorALAN D. T. BARRETT, ALAN D. T. BARRETT WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USASearch for more papers by this author DAVID W. C. BEASLEY, Corresponding Author DAVID W. C. BEASLEY WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USAAddress for correspondence: David W. C. Beasley, Department of Pathology, University of Texas Medical Branch, Galveston, TX 777555-0609. Voice: 409-772- 2547; fax: 409-747-2415; dwbeasle@utmb.edu.Search for more papers by this authorLI LI, LI LI WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USASearch for more papers by this authorMIGUEL T. SUDERMAN, MIGUEL T. SUDERMAN WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USASearch for more papers by this authorALAN D. T. BARRETT, ALAN D. T. BARRETT WHO Collaborating Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USASearch for more papers by this author First published: 25 January 2006 https://doi.org/10.1111/j.1749-6632.2001.tb02710.xCitations: 23Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume951, Issue1WEST NILE VIRUS: DETECTION, SURVEILLANCE, AND CONTROLDecember 2001Pages 332-335 RelatedInformation

Deer tick virus (DTV) is a recently recognized North American virus isolated from Ixodes dammini ticks. Nucleotide sequencing of fragments of structural and non-structural protein genes suggested that this virus was most closely related to the tick-borne flavivirus Powassan (POW), which causes potentially fatal encephalitis in humans. To determine whether DTV represents a new and distinct member of the Flavivirus genus of the family Flaviviridae, we sequenced the structural protein genes and 5′ and 3′ non-coding regions of this virus. In addition, we compared the reactivity of DTV and POW in hemagglutination inhibition tests with a panel of polyclonal and monoclonal antisera, and performed cross-neutralization experiments using anti-DTV antisera. Nucleotide sequencing revealed a high degree of homology between DTV and POW at both nucleotide (>80% homology) and amino acid (>90% homology) levels, and the two viruses were indistinguishable in serological assays and mouse neuroinvasiveness. On the basis of these results, we suggest that DTV should be classified as a genotype of POW virus.

This study of the yellow fever French neurotropic vaccine strain from the Institut Pasteur (FNV-IP) demonstrates that this viral genome is not as stable as that of the 17D-204 vaccine virus. FNV-IP was plaque-purified three times and then passaged eight times in Vero cells. Viral populations from the second and eighth passage post purification were sequenced and compared to the published sequences of FNV-IP. The passage-2 viral population had 31 nucleotide and nine amino acid changes compared to the parental virus while the passage-8 virus had six additional nucleotide changes encoding a single amino acid substitution. The plaque-purified virus also had two sequence deletions in the 3′-noncoding region. The plaque purification resulted in selection of a passage-2 virus that had a mouse LD50 of 20 pfu/ml, 67-fold greater than parental FNV-IP which had an LD50 of 0.3 pfu/ml. Subsequent passage in Vero cells resulted in a passage-8 virus which had increased neurovirulence with an LD50 of 3.2 pfu/ml. The only amino acid difference between the passage-2 and passage-8 viruses was at amino acid 638 of NS5 which lies within domain V of the RNA-dependent-RNA polymerase. Overall, these data indicate that FNV-IP virus has an inherently less stable genome than 17D vaccine virus and a variable viral population.