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At least 379 records · Page 21Linked to original sources
PubMed2004

Distinct patterns of natural selection in the reverse transcriptase gene of HIV-1 in the presence and absence of antiretroviral therapy.

The emergence of human immunodeficiency virus (HIV) drug-resistant mutations during antiretroviral therapy is explained by either the preexistence of low-frequency-resistant strains before the start of therapy or by the selection of unsuppressed resistant strains during therapy. We used pairwise and maximum likelihood analyses of the ratio of nonsynonymous to synonymous substitutions per site (d(N)/d(S)) to study the extent of positive selection in the reverse transcriptase (RT) gene of HIV-1 from multiple data sets of drug-treated (117 sequences) and drug-naive patients (270 sequences). In the pairwise analysis, evidence for positive selection (d(N)/d(S) > 1) was only found in drug-treated individuals and in codons conferring drug resistance. By the maximum likelihood method, a positive selection at codons conferring drug resistance was only observed in patients receiving therapy, and although positive selection was detected in drug-naive patients, this was always at codons unrelated to drug resistance. We therefore document a striking difference in the process of allele fixation in drug resistance codons (RC) between populations of HIV-1-infected individuals naive to treatment and those receiving therapy. Furthermore, although mutations associated with drug resistance are sometimes found in drug-naive patients, we suggest that these are fixed because of linkage to sites experiencing immune escape. Finally, we show that compensatory changes are likely to be important in the development of HIV drug resistance by counter-acting the deleterious effects normally associated with drug resistance mutations.

Amino Acid Sequence↗
PubMed2006

Genes of murine cytomegalovirus exist as a number of distinct genotypes.

Murine cytomegaloviruses encode a number of genes which modulate polymorphic host immune responses. We suggest that these viral genes should themselves therefore exhibit sequence polymorphism. Additionally, clinical isolates of human cytomegalovirus (HCMV) have been shown to vary extensively from the common laboratory strains. Almost all research conducted on murine cytomegalovirus (MCMV) has used the laboratory strains Smith and K181, which have been extensively passaged in vitro and in vivo since isolation. Using the heteroduplex mobility assay (HMA) to determine levels of sequence variation 11 MCMV genes were examined from 26 isolates of MCMV from wild mice, as well as both laboratory strains. Both the HMA and sequencing of selected genes demonstrated that whilst certain genes (M33, mck-2, m147.5, m152) were highly conserved, others (m04, m06, M44, m138, m144, m145 and m155) contained significant sequence variation. Several of these genes (m06, m144 and m155) exist in wild MCMV strains as one of several distinct genotypes.

Animals↗
PubMed1999

Molecular characterization and module composition of P22-related Salmonella phage genomes.

Genomes of newly isolated Salmonella phages were analysed by comparison of their EcoRI restriction patterns and by hybridization. Characteristic hybridization probes from reference phages P22, ES18 and E. coli phage lambda were chosen. Four probes selected from the lysis region examined the dispersal of the lambdoid lysis genes. Other probes characterized were the replication genes and part of the structural genes. The complex immunity region was investigated by means of hybridization as well as biological tests. The results showed the relationship of the isolated phages to the P22 branch of the lambdoid phages and revealed their modular genome organization consisting of different proportions of P22-related sequences. DNA restriction patterns of phages released from Salmonella strains sampled in limited geographical areas were significantly less heterogeneous than those of phages released from the worldwide sampled SARA collection. The use of prophage restriction patterns as a tool for the typing of Salmonellae to support the epidemiologic classification of pathogenic strains is discussed.

Bacteriophage P22↗
PubMed1998

Changes in H3 influenza A virus receptor specificity during replication in humans.

Influenza A viruses of the H3 subtype caused the 1968 Hong Kong pandemic, the hemagglutinin (HA) gene being introduced into humans following a reassortment event with an avian virus. Receptor specificity and serum inhibitor sensitivity of the HA of influenza A viruses are linked to the host species. Human H3 viruses preferentially recognize N-acetyl sialic acid linked to galactose by alpha2,6 linkages (Neu5Acalpha2,6Gal) and are sensitive to serum inhibitors, whereas avian and equine viruses preferentially recognize Neu5Acalpha2,3Gal linkages and are resistant to serum inhibitors. We have examined the receptor specificity and serum inhibitor sensitivity of H3 human influenza A viruses from the time they were introduced into the human population to gain insight into the mechanism of viral molecular evolution and host tropism. All of the viruses were sensitive to neutralization and hemagglutination inhibition by horse serum. Early H3 viruses were resistant to pig and rabbit serum inhibitors. Viruses isolated after 1977 were uniformly sensitive to inhibition by pig and rabbit sera. The recognition of Neu5Acalpha2,3Gal or Neu5Acalpha2,6Gal linkages was not correlated with the serum sensitivity. These data showed that the receptor specificity of HA, measured as inhibitor sensitivity, has changed during replication in humans since its introduction from an avian virus.

Amino Acid Sequence↗
PubMed1998

Identification of a thymidylate synthase gene within the genome of Chilo iridescent virus.

The thymidylate synthase (TS, EC 2.1.1.45) is essential for the de novo synthesis of dTMP in pro- and eucaryotic organisms. Consequently it plays a major role in the replication of the DNA genome of a cell or a DNA virus. The gene encoding the TS of Chilo iridescent virus (CIV) was identified by nucleotide sequence analysis of the viral genome and was mapped within the EcoRI CIV DNA fragments G and R. Computer assisted analysis of the DNA nucleotide sequence between the genome coordinates 0.482 and 0.489 revealed an open reading frame (ORF) of 885 nucleotides. This ORF was found to encode a polypeptide of 295 amino acid residues (33.9 kDa) that showed significant homologies to known TS of different species including mammals, plants, fungi, protozoa, bacteria, and DNA viruses. The highest amino acid homologies were found between the CIV-TS and the TS of herpesvirus ateles (54.0%), Saccharomyces cerevisiae (51.8%), herpesvirus saimiri (51.0%), rhesus monkey rhadinovirus (50.7%), mouse (50.5%), rat (50.2%), varicella-zoster virus (50.2%), equine herpesvirus 2 (50.0%), and the human TS (48.4%). The CIV-TS contains six amino acid domains that are highly conserved in the TS of other species. Within these domains the major amino acid residues are present for which a functional role has been reported. The CIV-TS was found to be more closely related to the TS of eucaryotes than to the TS of procaryotes indicating the phylogenetic origin of the CIV-TS gene. The identification of a TS gene in the genome of CIV is the first report of a viral TS that is not encoded by a herpesvirus or a bacteriophage.

Amino Acid Sequence↗
PubMed2001

Identification and in vivo characterization of the Epiphyas postvittana nucleopolyhedrovirus Ecdysteroid UDP-glucosyltransferase.

The genome of Epiphyas postvittana Nucleopolyhedrovirus (EppoMNPV) contains an ecdysteroid UDP-glucosyltransferase (egt) gene. The egt gene was completely sequenced and surrounding open reading frames identified. EppoMNPV egt is 1479 nucleotides in length encoding a protein with a predicted molecular mass of 55 kDa. Analysis of upstream sequence revealed dual TATA boxes and two CGT upstream activating region motifs. Mapping of the 5' terminus of the egt transcript identified a major transcript produced from an adenine residue 29 nucleotides downstream from the distal TATA box. No transcript was detected from a late promoter motif (GTAAG). Characterization of egt transcripts showed that poly-adenylation occurs at the 3' terminus. EppoMNPV egt transcripts were first detected in infected Epiphyas postvittana larvae by Northern hybridization at 9 h post-infection (hpi) and EGT enzyme activity was detected at 9 hpi in haemolymph from infected larvae. EppoMNPV EGT can conjugate the sugars from both UDP-glucose and UDP-galactose to ecdysone in vitro. Localization assays performed using radiolabelled ecdysone demonstrated that the conjugation of glucose or galactose, from the respective UDP-sugar, led to the prevention of the uptake of ecdysone by SF-21 cells. We propose that EGT functions to prevent the uptake of ecdysone or 20-hydroxyecdysone by metabolite and target cells respectively.

Amino Acid Sequence↗
PubMed2004

Peculiarities of herpes simplex virus (HSV) transcription: an overview.

The herpes simplex virus (HSV) has a 152 kbp dsDNA encoding probably 84 proteins. The approximate number of ORFs is 94, from which seven are doubled. The most probable number of single copy ORFs is 84 after omitting the two latency associated transcripts (LAT)/ORFs and the putative UL27.5 ORF. The high gene number creates a "crowded" genome with several overlapping transcripts. The unique long (U(L)) segment has at least 10 interposed ORFs, the existence of which was not obvious at first sequence analysis, while the unique short (U(S)) segment has two such genes. The surplus of ORFs causes complex transcription patterns: (1) Transcripts with common initiation signals but different termination; (2) Transcripts with different initiation sites but co-terminal ends; (3) "Nested" transcripts differing at both, the initiation as well as termination signals, having partially collinear sequences. At least three or possibly four ORF (gene) pairs (UL9.5/UL10; UL27/UL27.5; UL43/UL43.5; ICP34.5/ORF P and O) occupy both DNA strands at complementary positions rising anti-sense transcripts expressed by an antagonistic mechanism of mutual exclusion. The anti-sense mRNA mechanism might also operate when either LAT or ICP0 ORFs are expressed during latency assuring the absence of lytic virus replication. In contrast, during productive replication the cascade regulation of gene expression predominates, based on stepwise activation of immediate early (IE), early (E), early late (EL) and late (L) promoters. The promoters of different expression kinetic classes (alpha, beta, gamma-1 and gamma-2) are equipped with different number of cellular transcription factor binding and/or enhancer motifs. Surprisingly, only a few HSV mRNAs are being spliced (ICP0, UL15, US1, US12/ICP47). As reviewed here, the transcription pattern of the great majority of overlapping ORFs within the HSV-1 was quite convincingly elucidated, with exception of the putative UL27.5 gene. The UL27.5 transcript was not identified yet. Since the existence of the UL27.5 gene was based on indirect rather than direct evidence, it needs final confirmation.

Base Sequence↗
PubMed2000

Genomic and molecular evolutionary analysis of a newly identified infectious agent (SEN virus) and its relationship to the TT virus family.

A new group of transmissible single-stranded (ss) DNA viruses (SENV) distantly related to the large TT virus (TTV) family was recently identified. Eight different SENV isolates have been found, some with an association with posttransfusion hepatitis. A phylogenetic analysis of near-complete open-reading frame 1, including conserved motifs and excluding recombinant regions, was performed. The analysis used TTV-like minivirus as an outgroup, to determine a root of the phylogenetic tree, and compared 8 SENV isolates, 6 prototype TTV isolates, and 7 TTV variants (including SANBAN, TUS01, PMV, and YONBAN). Four distinct clusters separated by a bootstrap value of 100% were observed. YONBAN isolates formed a distinct outer group, representing the earliest recognized phylogenetic divergence (group 1). Prototype TTV formed group 2, PMV formed group 3, and SENV, SANBAN, and TUS01 isolates formed group 4, the most recently evolved group. This taxonomic classification suggests that these circular ssDNA viruses probably evolved from a common ancestor virus.

Amino Acid Sequence↗
PubMed1998

Intragenic variability of human cytomegalovirus glycoprotein B in clinical strains.

Human cytomegalovirus (HCMV) strains can be classified into four glycoprotein B (gB) genotypes, and there has been evidence of differences in viral virulence. In this study, intragenic variability of HCMV gB strains was analyzed. The gB gene was amplified by nested polymerase chain reaction using samples from immunosuppressed patients. The genotype of fragments corresponding to the cleavage site of gB was determined by restriction fragment analysis; fragments corresponding to the N- and C-termini (gBn and gBc) were sequenced and compared with published sequences. At the cleavage site, the four known genotypes were found. Typing revealed four major genotypes at the N-terminus and two at the C-terminus. In 22 of 44 strains, the gB type determined at the cleavage site was different from the gBn or gBc type (or either), indicating that intragenic variability within the gB gene occurs frequently.

Base Sequence↗
PubMed2001

Profiles of adaptation in two similar viruses.

The related bacteriophages phiX174 and G4 were adapted to the inhibitory temperature of 44 degrees and monitored for nucleotide changes throughout the genome. Phage were evolved by serial transfer at low multiplicity of infection on rapidly dividing bacteria to select genotypes with the fastest rates of reproduction. Both phage showed overall greater fitness effects per substitution during the early stages of adaptation. The fitness of phiX174 improved from -0.7 to 5.6 doublings of phage concentration per generation. Five missense mutations were observed. The earliest two mutations accounted for 85% of the ultimate fitness gain. In contrast, G4 required adaptation to the intermediate temperature of 41.5 degrees before it could be maintained at 44 degrees. Its fitness at 44 degrees increased from -2.7 to 3.2, nearly the same net gain as in phiX174, but with three times the opportunity for adaptation. Seventeen mutations were observed in G4: 14 missense, 2 silent, and 1 intergenic. The first 3 missense substitutions accounted for over half the ultimate fitness increase. Although the expected pattern of periodic selective sweeps was the most common one for both phage, some mutations were lost after becoming frequent, and long-term polymorphism was observed. This study provides the greatest detail yet in combining fitness profiles with the underlying pattern of genetic changes, and the results support recent theories on the range of fitness effects of substitutions fixed during adaptation.

Bacteriophage phi X 174↗
PubMed1999

Analyses of TT virus full-length genomic sequences.

Since the identification of TT virus, only one full-length and two near full-length sequences representing a single subtype of the virus have been reported. In order to understand further the nature of the TT virus genome, nine of the most divergent TT virus sequences have been extended to full-length or near full-length. Phylogenetic analysis demonstrated that these sequences represent three distinct TT virus genotypes and two subtypes. A high degree of nucleotide sequence variability (approximately 30%) was observed across the genomes with several significantly more divergent regions. Three conserved ORFs were identified, none of which shared significant amino acid sequence identity to sequences present in public databases. Additionally, sequence motifs, such as those necessary for protein translation and for rolling circle replication, were found to be partially conserved between all TT virus isolates.

DNA Viruses↗
PubMed2000

Phylogenetic position of the Diadromus pulchellus ascovirus DNA polymerase among viruses with large double-stranded DNA genomes.

The ASCOVIRIDAE: is a family of large double-stranded (ds) DNA insect viruses that contains four species, the Spodoptera frugiperda (SfAV1), Trichoplusia ni (TnAV2), Heliothis virescens (HvAV3) and Diadromus pulchellus (DpAV4) ascoviruses. These are unique among insect viruses in that the primary means of transmission among their lepidopteran hosts is generally by being vectored mechanically by hymenopteran parasitoids. Ascoviruses are similar in virion structure, but their relationships with their parasitoid vectors vary from being opportunistic to obligate. Little is known, however, about the relatedness of these viruses to one another or to other large dsDNA viruses. We therefore cloned and sequenced the delta DNA polymerase gene of DpAV4, characterized it and compared it to 59 eukaryotic and viral delta and epsilon DNA polymerases. Phylogenetic analyses based on these genes revealed that the ascoviruses DpAV4 and SfAV1 formed a group of virus species distinct from, but closely related to, species of the family IRIDOVIRIDAE: Detailed analyses of the relatedness of ascovirus species based on conserved delta DNA polymerase motifs showed two groups within the family ASCOVIRIDAE:, one containing DpAV4 and the other containing SfAV1, TnAV2 and HvAV3, which was consistent with their host-vector relationships. Despite significant differences in capsid symmetry between ascoviruses and iridoviruses, these results suggest that these viruses may have originated from a common ancestral virus.

Amino Acid Sequence↗
PubMed2006

Gene organization and complete sequence of the Hyphantria cunea nucleopolyhedrovirus genome.

The whole-genome sequence of the Hyphantria cunea nucleopolyhedrovirus (HycuNPV) was analysed. The entire nucleotide sequence of the HycuNPV genome was 132 959 bp long, with a G+C content of 45.1 mol%. A total of 148 open reading frames (ORFs) consisting of more than 50 aa were encoded by the genome. HycuNPV shares more than 122 ORFs with other lepidopteran group I NPVs, including Autographa californica MNPV, Bombyx mori NPV, Choristoneura fumiferana MNPV (CfMNPV), Choristoneura fumiferana defective NPV, Epiphyas postvittana MNPV and Orgyia pseudotsugata MNPV (OpMNPV). Six ORFs are identified as being unique to HycuNPV. Most of the HycuNPV ORFs showed higher similarity to CfMNPV and OpMNPV ORFs than to those of the other group I NPVs. HycuNPV encodes two conotoxin-like homologues (ctls), which are observed only in OpMNPV in group I NPVs. HycuNPV encodes three inhibitors of apoptosis (iaps), hycu-iap-1, hycu-iap-2 and hycu-iap-3, a feature that it shares only with CfMNPV. In addition, six homologous regions (hrs) are identified in the HycuNPV genome. These hrs are located in regions similar to those of the OpMNPV hrs, but different from most of the CfMNPV hrs. Based on the close phylogenetic relationship and conservation of group I NPV-specific genes, such as gp64, ie-2 and ptp-1, it is concluded that HycuNPV belongs to the group I NPVs and is most similar to CfMNPV or OpMNPV.

Amino Acid Sequence↗
PubMed1999

Comparative analysis of evolutionary mechanisms of the hemagglutinin and three internal protein genes of influenza B virus: multiple cocirculating lineages and frequent reassortment of the NP, M, and NS genes.

Phylogenetic profiles of the genes coding for the hemagglutinin (HA) protein, nucleoprotein (NP), matrix (M) protein, and nonstructural (NS) proteins of influenza B viruses isolated from 1940 to 1998 were analyzed in a parallel manner in order to understand the evolutionary mechanisms of these viruses. Unlike human influenza A (H3N2) viruses, the evolutionary pathways of all four genes of recent influenza B viruses revealed similar patterns of genetic divergence into two major lineages. Although evolutionary rates of the HA, NP, M, and NS genes of influenza B viruses were estimated to be generally lower than those of human influenza A viruses, genes of influenza B viruses demonstrated complex phylogenetic patterns, indicating alternative mechanisms for generation of virus variability. Topologies of the evolutionary trees of each gene were determined to be quite distinct from one another, showing that these genes were evolving in an independent manner. Furthermore, variable topologies were apparently the result of frequent genetic exchange among cocirculating epidemic viruses. Evolutionary analysis done in the present study provided further evidence for cocirculation of multiple lineages as well as sequestering and reemergence of phylogenetic lineages of the internal genes. In addition, comparison of deduced amino acid sequences revealed a novel amino acid deletion in the HA1 domain of the HA protein of recent isolates from 1998 belonging to the B/Yamagata/16/88-like lineage. It thus became apparent that, despite lower evolutionary rates, influenza B viruses were able to generate genetic diversity among circulating viruses through a combination of evolutionary mechanisms involving cocirculating lineages and genetic reassortment by which new variants with distinct gene constellations emerged.

Base Sequence↗