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Cospeciation and horizontal transmission of avian sarcoma and leukosis virus gag genes in galliform birds.

In a study of the evolution and distribution of avian retroviruses, we found avian sarcoma and leukosis virus (ASLV) gag genes in 26 species of galliform birds from North America, Central America, eastern Europe, Asia, and Africa. Nineteen of the 26 host species from whom ASLVs were sequenced were not previously known to contain ASLVs. We assessed congruence between ASLV phylogenies based on a total of 110 gag gene sequences and ASLV-host phylogenies based on mitochondrial 12S ribosomal DNA and ND2 sequences to infer coevolutionary history for ASLVs and their hosts. Widespread distribution of ASLVs among diverse, endemic galliform host species suggests an ancient association. Congruent ASLV and host phylogenies for two species of Perdix, two species of Gallus, and Lagopus lagopus and L. mutus also indicate an old association with vertical transmission and cospeciation for these ASLVs and hosts. An inference of horizontal transmission of ASLVs among some members of the Tetraoninae subfamily (grouse and ptarmigan) is supported by ASLV monophyletic groups reflecting geographic distribution and proximity of hosts rather than host species phylogeny. We provide a preliminary phylogenetic taxonomy for the new ASLVs, in which named taxa denote monophyletic groups.

Animals↗

The panorama of the diversity of H5 subtype influenza viruses.

To elucidate the global diversity of H5 influenza viruses from a dynamic view, haemagglutinin (HA) sequences of 170 isolates were selected and analyzed in this study. Our results showed that H5 influenza isolates could be divided into two distinct lineages that circulated in the Eastern Hemisphere and the Western Hemisphere, respectively. This may be due to the separate migration routes and habitats of birds in the two hemispheres. The two distinct lineages, having existed at least for decades, possibly began divergence in 1850s. Each of the two distinct HA lineages could be further divided into some sublineages, but there was little correlation between the minor lineages and their isolation places, isolation time, neuraminidase subtypes, host species or virulence. The panorama of the diversity of H5 influenza viruses presented here integrated all known H5 epidemics including the current severe H5N1 avian epidemics in the Eastern Hemisphere and suggested that H5 virulent viruses could originate from multiple sublineages and associate with multiple NA subtypes. Our study provided a framework for the studies on the evolution and epidemiology of H5 influenza viruses.

Genetic Variation↗

Analysis of intratypic variation evident in an Ibaraki virus strain and its epizootic hemorrhagic disease virus serogroup.

A new strain of Ibaraki virus (IBAV) was isolated from cattle showing atypical symptoms of Ibaraki disease. The isolate was genetically characterized, and the genetic diversity and evolution of the capsid proteins of viruses in the epizootic hemorrhagic disease virus (EHDV) serogroup were investigated. The nucleotide sequences of the isolate's viral RNA segments 2, 3, 6, and 7, which encode the viral structural proteins VP2, VP3, VP5, and VP7, respectively, were determined and were then compared against those of the existing strains of IBAV and EHDV, to which IBAV belongs serologically. The nucleotide sequences of segments 3 and 7 were conserved within the EHDV serogroup, particularly well among the strains of IBAV and Australian EHDV. The similarity of the sequence of segment 6 of the isolate to sequences of corresponding segments of the other strains of IBAV and EHDV was found to be about 93%. The similarity of segment 2 of the isolate to segments 2 of the other strains of IBAV and EHDV was less than 70%. Phylogenetic analysis based on the deduced amino acid sequences of segments 3 and 7 revealed that the viruses differed according to their geographical distributions. However, the new isolate of IBAV was categorized as having a distinct lineage in the phylogenetic tree of VP2. These results suggest that the isolate was modified by a reassortment of segment 2 and that it exhibits unique genetic and antigenic characteristics.

Animals↗

Poliovirus persistence in human cells in vitro.

Poliovirus (PV) can persist in vivo in the intestine of immunocompromised hosts for years. Moreover, immunocompetent individuals who have survived paralytic poliomyelitis sometimes develop the post-poliomyelitis syndrome (PPS), consisting of a variety of symptoms including new muscular atrophies. PPS may be due to PV persistence. We have developed models of PV persistence in neural cells and epidermoid cells. Cell determinants are of crucial importance for the establishment of persistent infections in human neuronal cells, whereas viral determinants play the primary role in human epidermoid HEp-2 cells. The results obtained with these in vitro models show the capacity of PV to persist and reveal a virus and cell co-evolution involving PV-receptor interactions. In addition, they suggest that several mechanisms are used by PV to establish and maintain persistent infections.

Animals↗

Evolution of viral quasispecies in interferon-treated patients with chronic hepatitis C virus infection.

BACKGROUND/AIMS: To evaluate whether interferon treatment failure/relapse is related to changes in hepatitis C virus quasispecies complexity (number of variants) or diversity (genetic relatedness of variants). METHODS: We analyzed hypervariable region heterogeneity in hepatitis C virus-infected patients by heteroduplex mobility assay and by phylogenetic analysis of sequenced clones. Sera from 11 patients were tested. Response was defined biochemically and virologically. Patients were treated with 3 or 6 MIU interferon for 6 months and followed up for 6 months. Four patients were non-responders, four were transient responders and three untreated patients served as controls. Three time points were studied for the non-responders (pre-interferon, end of interferon, end of 6 months of follow-up), two for the transient responders (pre-interferon and post follow-up) and two for the controls (1 year apart). A total of 260 clones were examined by heteroduplex mobility assay and 144 clones were sequenced. RESULTS: A linear correlation between heteroduplex mobility and nucleotide substitutions was observed, validating this method for assessment of quasispecies diversity. Although complexity at each time point was similar in all groups, diversity increased significantly with interferon treatment. The percentage of new variants in follow up was significantly higher in non-responders than in controls. These new variants exhibited a greater change in heteroduplex mobility, a higher percentage of changes in amino acids in non-responders compared to controls and were found to cluster separately from pretreatment variants when analyzed phylogenetically. These changes were less marked in transient responders. CONCLUSIONS: These mutations may allow hepatitis C virus to escape antiviral effects of interferon therapy.

Amino Acid Sequence↗

Transmission of equine influenza virus to dogs.

Molecular and antigenic analyses of three influenza viruses isolated from outbreaks of severe respiratory disease in racing greyhounds revealed that they are closely related to H3N8 equine influenza virus. Phylogenetic analysis indicated that the canine influenza virus genomes form a monophyletic group, consistent with a single interspecies virus transfer. Molecular changes in the hemagglutinin suggested adaptive evolution in the new host. The etiologic role of this virus in respiratory disease was supported by the temporal association of rising antibody titers with disease and by experimental inoculation studies. The geographic expansion of the infection and its persistence for several years indicate efficient transmission of canine influenza virus among greyhounds. Evidence of infection in pet dogs suggests that this infection may also become enzootic in this population.

Amino Acid Sequence↗

Polyoma virus DNA: complete nucleotide sequence of the gene which codes for polyoma virus capsid protein VP1 and overlaps the VP2/VP3 genes.

The nucleotide sequence of part of the late region of the polyoma virus genome was determined. It contains coding information for the major capsid protein VP1 and the C-terminal region of the minor proteins VP2 and VP3. In the sequence with the same polarity as late mRNA's, all coding frames are blocked by termination codons in a region around 48 units on the physical map. This is the region where the N-terminus of VP1 and the C-termini of VP2 and VP3 have been located (T. Hunter and W. Gibson, J. Virol. 28:240-253, 1978; S. G. Siddell and A. E. Smith, J. Virol. 27:427-431, 1978; Smith et al., Cell 9:481-487, 1976). There are two long uninterrupted coding frames in the late region of polyoma virus DNA. One lies at the 5' end of the sequence and contains potential coding sequences for VP2 and VP3. The other contains 383 consecutive sense codons starting with the ATG at nucleotide position 1,218, extends from 47.5 to 25.8 units counterclockwise on the physical map, and is located where the VP1 gene has been mapped. The VP1 gene overlaps the genes for proteins VP2/VP3 by 32 nucleotides and uses a different coding frame. From the DNA sequence, the amino acid sequence of VP1 was predicted. The proposed VP1 sequence is in good agreement with other data, namely, with the partial N-terminal amino acid sequence and the total amino acid composition. The VP1 coding frame terminates with a TAA codon at 25.8 map units. This is followed by an AATAAA sequence, which may act as a processing signal for the viral late mRNA's. When both nucleotide and amino acid sequences are compared with their counterparts in the related simian virus 40, extensive homologies are found over the entire region of the two viral genomes. Maximum homology appears to occur in those regions which code for the C-termini of the VP1 proteins. The overlap region of VP1 with VP2/VP3 of polyoma virus is shorter by 90 nucleotides than is that of simian virus 40 and shows very limited homology with the simian virus 40 sequence. This leads to the suggestion that the overlap segments of both viruses have been freed from stringency imposed on drifting during evolution and that proteins VP2 and VP3 of polyoma virus may have been truncated by the appearance of a termination codon within the sequence.

Amino Acid Sequence↗

Blood donor testing for HIV-I/II and HTLV-I/II.

In 1985, serologic testing became available to screen blood donors for the viruses associated with the acquired immunodeficiency syndrome; these viruses are now called human immunodeficiency viruses I and II. In 1989, blood donor screening for other retroviruses, human T-cell lymphotropic viruses I and II, was initiated. This article describes the evolution of testing protocols for blood donors for these viruses, disease manifestations associated with seropositivity, the efficacy of donor screening including testing for these retroviruses, and counseling recommendations for positive blood donors with confirmed infection.

Blood Donors↗

[Epidemiology of hepatitis C virus infection in 1,304 HCV positive patients: variations according to the origin of transmission and year of diagnosis].

UNLABELLED: The evolution of epidemiological data on hepatitis C virus infection is poorly documented and thus the impact of screening is difficult to evaluate. AIM: To study epidemiological variations based on the origin of transmission and the year of diagnosis of hepatitis C virus infection. METHODS: The files of all 1304 patients seen in the hepatology unit of the Rennes University Hospital were analyzed (retrospectively before and prospectively after October 1995) in relation to epidemiological features. RESULTS: Despite widespread screening which is the source of 60% of the diagnoses, the total number of new cases of hepatitis C infection per year has not increased. Compared to patients diagnosed in the first years following the discovery of the virus, patients recently identified were younger (42 +/- 14 years) and frequently drug addicts (40%). Aminotransaminases were normal in 20% of cases. The frequency of cirrhosis has declined (17%). There has been a decrease in the proportion of patients who undergo liver biopsy (50%) and treatment with interferon (one third of patients). CONCLUSIONS: The impact of screening on the number of newly treated patients seems to be lower than previously predicted.

Adult↗

Impact of human immunodeficiency virus type 1 (HIV-1) genetic diversity on performance of four commercial viral load assays: LCx HIV RNA Quantitative, AMPLICOR HIV-1 MONITOR v1.5, VERSANT HIV-1 RNA 3.0, and NucliSens HIV-1 QT.

Human immunodeficiency virus type 1 (HIV-1) evolution and changing strain distribution present a challenge to nucleic acid-based assays. Reliable patient monitoring of viral loads requires the detection and accurate quantification of genetically diverse HIV-1. A panel of 97 HIV-1-seropositive plasma samples collected from Cameroon, Brazil, and South Africa was used to compare the performance of four commercially available HIV RNA quantitative tests: Abbott LCx HIV RNA Quantitative assay (LCx), Bayer Versant HIV-1 RNA 3.0 (bDNA), Roche AMPLICOR HIV-1 MONITOR v1.5 (Monitor v1.5), and bioMérieux NucliSens HIV-1 QT (NucliSens). The panel included group M, group O, and recombinant viruses based on sequence analysis of gag p24, pol integrase, and env gp41. The LCx HIV assay quantified viral RNA in 97 (100%) of the samples. In comparison, bDNA, Monitor v1.5, and NucliSens quantified viral RNA in 96.9%, 94.8%, and 88.6% of the samples, respectively. The two group O specimens were quantified only by the LCx HIV assay. Analysis of nucleotide mismatches at the primer/probe binding sites for Monitor v1.5, NucliSens, and LCx assays revealed that performance characteristics reflected differences in the level of genetic conservation within the target regions.

Genetic Variation↗

Analyses on mutation patterns, detection of population bottlenecks, and suggestion of deleterious-compensatory evolution among members of the genus Potyvirus.

Viruses of the family Potyviridae exhibited a robust single-nucleotide polymorphism profile at the between-species level, conforming to the neutral theory rule. However, the ratios of nonsynonymous to synonymous mutations (Ka/Ks) were relatively greater between-species than within-species in viral cistrons examined from members of the genus Potyvirus, indicating a relaxation on constraint. Judged by the McDonald and Kreitman's test, the fixation frequencies for nonsynonymous mutations across the genomes of closely related potyviruses were greater than expected, suggesting population bottlenecks at speciation. These mutation patterns are best explained by a deleterious-compensatory model.

Animals↗

Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins.

Retroviral entry into cells depends on envelope glycoproteins, whereby receptor binding to the surface-exposed subunit triggers membrane fusion by the transmembrane protein (TM) subunit. We determined the crystal structure at 2.5-A resolution of the ectodomain of gp21, the TM from human T cell leukemia virus type 1. The gp21 fragment was crystallized as a maltose-binding protein chimera, and the maltose-binding protein domain was used to solve the initial phases by the method of molecular replacement. The structure of gp21 comprises an N-terminal trimeric coiled coil, an adjacent disulfide-bonded loop that stabilizes a chain reversal, and a C-terminal sequence structurally distinct from HIV type 1/simian immunodeficiency virus gp41 that packs against the coil in an extended antiparallel fashion. Comparison of the gp21 structure with the structures of other retroviral TMs contrasts the conserved nature of the coiled coil-forming region and adjacent disulfide-bonded loop with the variable nature of the C-terminal ectodomain segment. The structure points to these features having evolved to enable the dual roles of retroviral TMs: conserved fusion function and an ability to anchor diverse surface-exposed subunit structures to the virion envelope and infected cell surface. The structure of gp21 implies that the N-terminal fusion peptide is in close proximity to the C-terminal transmembrane domain and likely represents a postfusion conformation.

Amino Acid Sequence↗

Mutational trends in V3 loop protein sequences observed in different genetic lineages of human immunodeficiency virus type 1.

Highly variable international human immunodeficiency virus type 1 envelope sequences can be assigned to six major clades, or phylogenetically defined subtypes, designated A through F. These subtypes are approximately equidistant in terms of evolutionary distance measured by nucleotide sequences. This radiation from a common ancestral sequence may have been in step with the spread of the pandemic. In this study, V3 loop protein sequence relationships within these major clades are analyzed to determine how the different lineages might be evolving with respect to this biologically important domain. The V3 loop has been shown to influence viral phenotype and to elicit both humoral and cellular immune responses. To identify patterns in V3 loop amino acid evolution, we cluster the sequences by a phenetic principle which evaluates protein similarities on the basis of amino acid identities and similarities irrespective of evolutionary relationships. When phenetic clustering patterns are superimposed upon phylogenetic subtype classifications, two interesting mutational trends are revealed. First, a set of identical, or highly similar, V3 loop protein sequences can be identified within two otherwise dissimilar genetic subtypes, A and C. Second, the D subtype sequences are found to possess the most radically divergent set of V3 loop sequences. These and other patterns characteristic of the V3 loop reflect the acquisition of specific biological properties during the apparently recent evolution of the human immunodeficiency virus type 1 lineages.

Amino Acid Sequence↗

Evolution of T lymphocytes and cytokine expression in classical swine fever (CSF) virus infection.

This study characterized the cell-mediated immune response in pigs inoculated with the Alfort 187 isolate of classical swine fever (CSF) virus. Quantitative changes in the T-lymphocyte population (CD3(+), CD4(+) and CD8(+)) and qualitative changes in cytokine expression (IL-2, IL-4 and IFNgamma) by these cells in serum, thymus and spleen were demonstrated. These changes coincided spatially and temporally with previously described quantitative and qualitative changes in monocyte-macrophage populations, thus demonstrating the contribution of the two cell populations to lymphoid depletion. Moreover, examination of cytokine expression in thymus and spleen samples revealed a type 1 cell-mediated immune response in the early and middle stages of the experiment, giving way to a type 2 immune response towards the end of the experiment; these findings, which accorded with the serological results and lymphopenia, may influence the delayed humoral response characteristic of CSF.

Animals↗