Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “viral evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources
PubMed1999

Human immunodeficiency virus type 1 genetic evolution in patients with prolonged suppression of plasma viremia.

Treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with combination drug regimens results in a reduction of plasma viral load to levels below the limit of detection. To investigate the genomic fluctuations in HIV-1 populations from long-term responders to antiviral therapies we analyzed the viral sequence evolution of env and pol genes from sequential peripheral blood mononuclear cell (PBMC) DNA samples of three infected patients. Analyses of sequences covering the V3 and flanking env regions obtained from blood samples at the beginning of the therapy and at 14 or 24 months from baseline revealed that HIV-1 quasispecies continue to evolve in the three patients following combination antiretroviral therapy. Minor drug-resistant mutant subpopulations were also searched for and found in one patient. Interestingly, no minor resistant subpopulations were found in the other two patients despite the fact that they showed evidence of ongoing viral replication. Finally, the genetic analysis of the env gene shows a reduction in PBMC env viral population diversity after long-term response to the therapy in all the patients analyzed.

Anti-HIV Agents↗
PubMed2002

Viral interference with antigen presentation.

CD8+ T cells play an important role in immunity to viruses. Just how important these cells are is demonstrated by the evolution of viral strategies for blocking the generation or display of peptide-major histocompatibility complex class I complexes on the surfaces of virus-infected cells. Here, we focus on viral interference with antigen presentation; in particular we consider the importance (and difficulty) of establishing the evolutionary significance (that is, the ability to enhance viral transmission) of viral gene products that interfere with antigen presentation in vitro.

Animals↗
PubMed1998

Variability of antigenic epitopes of the fusion protein of Newcastle disease virus.

Using a panel of 10 monoclonal antibodies (Mab) against fusion (F) protein of Newcastle disease virus (NDV), strain Australia-Victoria, three non-overlapping antigenic sites (F1, F2 and F3) and one site partially overlapping with the sites F1 and F2 (F1.2) have been identified. The sites F2 and F3 are clusters that each include four antigenic epitopes. The antigenic stability of the above epitopes was estimated by comparison of the binding capacity of the corresponding Mabs towards 63 NDV strains isolated in different years and places from various avian species. The results demonstrated high variability of the site F1.2 and of all the four epitopes of the site F2. At the same time, the only epitope of the site F1 can be defined as highly conservative: the corresponding Mab gave positive binding with 60 from 63 NDV strains, one from the four epitopes pertaining to site F3 was the most conservative--the corresponding Mab reacted with all the 63 strains used in the studies, while the other three Mabs showed rather low stability--the corresponding Mabs reacted with 34-39 NDV strains. Thus, as opposed to the published data asserting antigenic stability of the F protein contrary to the high variability of the haemagglutinin-neuraminidase (HN) protein, our results have revealed a number of variable epitopes on the F protein. This demonstrates an evolutionary changeability of the F protein, which is of importance from the theoretical (viral antigenic evolution) as well as practical point of view.

Antibodies, Monoclonal↗
PubMed2003

Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy.

Recurrent hepatitis B virus (HBV) infection after liver transplantation can be prevented by prophylactic hepatitis B immune globulin (HBIG) and lamivudine therapy. However, reinfection may still occur due to the emergence of immune escape mutants and mutants of the YMDD motif. The full spectrum of mutations within the HBV genome during recurrent HBV infection remains to be documented. In this study, serial HBV isolates were characterized from a patient with lamivudine resistance prior to liver transplantation who developed recurrent HBV infection within 2 months of transplantation despite a high dose of HBIG and lamivudine therapy. Sequence analysis of full-length viral genome before transplantation revealed many point mutations as compared with a wild-type genotype C sequence, including the T1753G/A1762T/G1764A triple mutation in the basal core promoter and the G1896A nonsense mutation in the precore region. After transplantation and therapy, several point mutations in the HBV genome emerged or became dominant. These mutations caused L426I/L526M/M550I triple mutation (equivalent to L428I/L528M/M552I in previous reports) in the polymerase, and D144E mutation in the "a" determinant of HBsAg. Transfection experiments revealed that the D144E mutation reduced HBsAg affinity to anti-HBs, confirming its active role for immune escape. Our study suggests that mutations in the HBsAg (D144E) and the polymerase (L426I/L526M/M550I) of HBV genome may be responsible for viral breakthrough despite HBIG prophylaxis and lamivudine therapy.

Base Sequence↗
PubMed1998

Comparison of the rate of sequence variation in the hypervariable region of E2/NS1 region of hepatitis C virus in normal and hypogammaglobulinemic patients.

The hypervariable region (HVR) of the E2/NS1 region of hepatitis C virus (HCV) varies greatly between viral isolates with high rates of genomic change reported during the course of chronic infection. The HVR is thought to encode a structurally unconstrained envelope protein containing several linear B cell epitopes recognized by neutralizing antibody. It has been postulated that amino acid changes in the HVR could result from humoral immune pressure leading to the selection of escape mutants. The aim of this study was to compare the rates of nucleotide and amino acid variation in the HVR of control patients to patients with common variable immunodeficiency (CVID) where the effect of the humoral immune system is reduced. Five controls and four patients with CVID were studied. Serum samples were taken over periods of between 1 and 6 years. HCV was detected by polymerase chain reaction (PCR) with primers derived from conserved flanking regions of the HVR. PCR products were cloned into a plasmid vector and recombinant clones identified by restriction enzyme digestion. Purified DNA from at least three individual clones from each time point was sequenced by the dideoxynucleotide chain-termination method. Consensus sequences were extracted from the three clones, and the DNA and deduced protein sequences were compared. Control patients had a mean rate of nucleotide change of 6.954 nucleotide substitutions per year, compared with patients with CVID with a rate of 0.415 nucleotide substitutions per year (P < .02). The corresponding rates for amino acid variation were 3.868 amino acid substitutions per year for the control patients compared with 0.185 amino acid substitutions per year for the patients with CVID. These findings suggest that in the absence of humoral immune selective pressure, the frequency of occurrence of genetic variation in the major viral species is reduced. The mutations occur, but in the absence of immune selection remain as minor species. The evolution of viral mutants capable of evading the host's immune system may contribute to the ability of HCV to establish chronic infection.

Adult↗
PubMed2001

Molecular evolution of influenza A/H3N2 viruses in the province of Québec (Canada) during the 1997-2000 period.

In this study, we compared antigenic (hemagglutination inhibition (HI) assay) and molecular (sequencing of the hemagglutinin (HA1) gene) characterization of influenza isolates collected in the Province of Québec (Canada) during the last three flu seasons (1997-2000). Twenty-three isolates were tested by a standard HI assay and 37 by sequencing of the HA1 gene for their homology to the A/H3N2 vaccine strains A/Wuhan/359/95 (1997-1998) and A/Sydney/5/97 (1998-1999 and 1999-2000). By HI, two isolates were antigenically similar to A/Wuhan/359/95 (both from 1997 to 1998), 16 were similar to A/Sydney/5/97 (1997-2000) and no conclusions could be inferred for the other five isolates due to identical HI titers for the two vaccine strains (n=4) or insufficient viral titer (n=1). Sequence analysis revealed that four isolates from 1997 to 1998 were related to A/Wuhan/359/95 whereas the others (n=4) from 1997 to 1998, as well as all isolates from 1998 to 1999 (n=18) and 1999 to 2000 (n=11) were closer to A/Sydney/5/97. The mean number of amino acid differences for the 33 A/Sydney/5/97-like isolates compared with the homologous vaccine strain was 6.3 (1.9%), 9.2 (2.8%) and 13.6 (4.1%) for those collected in 1997-1998, 1998-1999, and 1999-2000, respectively. Phylogenetic analysis confirmed that a progressive drift occurred among our A/H3N2 influenza isolates over the last three flu seasons. Furthermore, it revealed that isolates collected during the last two flu seasons were in fact more related to A/Panama/2007/99 (2000-2001 vaccine strain) than to A/Sydney/5/97. Our studies suggest that molecular analysis of the HA1 gene should complement the HI assay for a more accurate analysis of influenza A virus drift.

Antigens, Viral↗
PubMed2005

Evolution of relative synonymous codon usage in Human Immunodeficiency Virus type-1.

Mutation in Human Immunodeficiency Virus type-1 (HIV-1) is extremely rapid, a consequence of a low-fidelity viral reverse transcription process. The envelope gene has been shown to accumulate substitutions at a rate of approximately 1% per year and can frequently spend a long time in the host (approximately 10 years). The relative synonymous codon usage (RSCU) in HIV-1 is known to be different from that of the human host. However, by reengineering the protein coding sequences of HIV-1 to reflect the RSCU patterns observed in humans, a large increase in protein expression is observed. It is reasonable to suggest that within a host there may be a selective drive for change in the RSCU of HIV-1 towards human RSCU. To test this hypothesis we analyzed HIV-1 partial envelope sequences from eight patients sampled serially in time. For each sequence, an RSCU table was constructed. Sequences were labelled as "early" or "late" depending on whether they were sampled before or after the mid-point of the study. Using the RSCU values as descriptor variables, a Principal Components Analysis (PCA) was performed. The first three components clearly discriminated between early and late sequences. We also constructed pooled groupwise RSCU tables for early and late sequences. The viral RSCU values of each of the groups were correlated with human RSCU. If there is selection for host-adaptation in RSCU, we expect that "late" viral RSCUs would tend to be more highly correlated with human RSCU than "early" viral RSCUs. In fact, tests of significance suggest that this is the case. However, closer examination of the data revealed that the apparent trend towards human RSCU can be attributed to the homogenization of the codon usage by mutation pressure rather than host adaptation.

Algorithms↗
PubMed1994

Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays.

High mutation rates and strong selective pressures imposed on human immunodeficiency viruses in vivo result in the formation of pools of genetic variants known as quasispecies. DNA heteroduplex mobility and tracking analyses were used to monitor the generation of HIV sequence diversity, to estimate quasispecies complexity, and to assess the turnover of genetic variants to approach an understanding of the relationship between viral quasispecies evolution in vivo and disease progression. Proviral DNA pools were nearly homogeneous soon after sexual transmission. The emergence and clearance of individual variants then occurred at different rates in different individuals. High quasispecies complexity was found in long-term-infected, asymptomatic individuals, while rapid CD4+ cell decline and AIDS were often, but not always, associated with lower quasispecies complexity. Proviral genetic variation was often low following in vitro culture, because of the outgrowth of one or a few variants that often became more abundant only later as proviruses in peripheral blood mononuclear cells. These studies provide insight into the dynamics of human immunodeficiency virus sequence changes in vivo and illustrate the utility of heteroduplex analysis for the study of phenomena associated with rapid genetic changes.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Bovine enteroviruses as indicators of fecal contamination.

Surface waters frequently have been contaminated with human enteric viruses, and it is likely that animal enteric viruses have contaminated surface waters also. Bovine enteroviruses (BEV), found in cattle worldwide, usually cause asymptomatic infections and are excreted in the feces of infected animals in large numbers. In this study, the prevalence and genotype of BEV in a closed herd of cattle were evaluated and compared with BEV found in animals in the immediate environment and in environmental specimens. BEV was found in feces from 76% of cattle, 38% of white-tailed deer, and one of three Canada geese sharing the same pastures, as well as the water obtained from animal watering tanks, from the pasture, from streams running from the pasture to an adjacent river, and from the river, which emptied into the Chesapeake Bay. Furthermore, BEV was found in oysters collected from that river downstream from the farm. These findings suggest that BEV could be used as an indicator of fecal pollution originating from animals (cattle and/or deer). Partial sequence analysis of the viral genomes indicates that different viral variants coexist in the same area. The possibility of identifying the viral strains found in the animals and in the contaminated areas by sequencing the RNA genome, could provide a tool to find the origin of the contamination and should be useful for epidemiological and viral molecular evolution studies.

Animals↗
PubMed1996

V3 seroreactivity and sequence variation: tracking the emergence of V3 genotypic variation in HIV-1-infected patients.

OBJECTIVE: To investigate the relationship between V3-specific immune responses and viral quasispecies evolution in 10 HIV-1-seropositive patients enrolled in a phase I trial of recombinant gp160. METHODS: Serologic responses to the HIVLAI V3 loop and autologous V3 loop DNA sequences were sequentially determined over a 3-4-year interval. RESULTS: Six patients either seroconverted or had a > or = 42-fold boost in titer to the V3 reagent associated with an average of 3.2 amino-acid changes in their autologous V3 loops. Four patients with < or = 11-fold change in titer to the V3 loop showed an average of 0.75 amino-acid changes. Attempts to measure autologous V3 loop responses in four patients using a peptide enzyme-linked immunosorbent assay technique did not show a distinct binding preference for autologous versus heterologous V3 loop peptides. Thus, we interpret seroreactivity to the heterologous HIVLAI V3 loop to reflect the broadness of the V3 immune response rather than a direct measure of epitope-specific immune pressure. CONCLUSIONS: These data suggest that the broadness of serologic responses to viral epitopes are reflected in the rate of evolution of their cognate coding sequences and support the view that the immune response to HIV-1 results in the continuous selection of new viral variants during the course of disease.

AIDS Vaccines↗
PubMed2001

Diverged evolution of recent equine-2 influenza (H3N8) viruses in the Western Hemisphere.

We reported previously that equine-2 influenza A virus (H3N8) had evolved into two genetically and antigenically distinct "Eurasian" and "American" lineages. Phylogenetic analysis, using the HA1 gene of more recent American isolates, indicated a further divergence of these viruses into three evolution lineages: A South American lineage, a Kentucky lineage, and a Florida lineage. These multiple evolution pathways were not due to geographic barriers, as viruses from different lineages co-circulated. For the Kentucky lineage, the evolution rate was estimated to be 0.89 amino acid substitutions per year, which agreed with the previously estimated rate of 0.8. For the South American lineage, the evolution rate was estimated to be only 0.27 amino acid substitutions per year. This low evolution rate was probably due to a unique alternating Ser138 to Ala138 substitutions at antigenic site A. For the Kentucky lineage, there was a preference for sequential nonsynonymous substitutions at antigenic site B, which was also a "hot spot" for amino acid substitutions. Convalescent sera had minimal cross-reactivity to viruses of different lineages, indicating antigenic distinctions among these viruses. In contrast to human H3N2 viruses, our results suggested that the evolution of equine-2 influenza virus resembled the multiple evolution pathways of influenza B virus.

Amino Acid Sequence↗
PubMed1996

Evolution of the haemagglutinin-esterase gene of influenza C virus.

The nucleotide sequences of the haemagglutinin-esterase (HE) genes of 18 influenza C virus strains isolated in Japan during the period from 1964 to 1988 (11 published and 7 new sequences) were analysed to examine their evolutionary relationships. The phylogenetic tree constructed by the maximum parsimony method revealed the existence of four discrete lineages (I to IV), one of which (lineage III) may have died out in the late 1970s. Sequential evolution was demonstrated within seven strains of lineage I, which allowed estimation of an evolutionary rate of 0.49 x 10-3 nucleotide substitutions per site per year, a value corresponding to about one-ninth of the rates of human influenza A virus haemagglutinin genes. In the previously proposed immunodominant region on HE protein (positions 178 to 217), there was little or no amino acid sequence divergence among viruses on the same lineage although considerable divergence was seen among those on different lineages, raising the possibility that immune selection may not have played a significant role in the evolution of the glycoprotein, at least not after separation into lineages occurred. It was also found that the HE genes of the seven isolates obtained outside Japan during 1966-1983 could be each assigned to one of lineages I, II and IV, which suggests that influenza C virus is capable of spreading worldwide.

Amino Acid Sequence↗
PubMed2006

Host mediated selection of pathogen genotypes as a mechanism for the maintenance of baculovirus diversity in the field.

The genetic diversity of many DNA virus populations in nature is unknown, but for those that have been studied it has been found to be relatively high. This is particularly true for baculoviruses, a family of large double-stranded DNA viruses that infect the larval stages of insects. Why there should be such heterogeneity within these virus populations is puzzling and what sustains it is still unknown. It has long been recognized that some baculoviruses have a relatively wide host range, but the effect of different host species on the genotypic structure of a baculovirus population has received little attention. We provide evidence that infection of different insect species can influence the genetic diversity of a Panolis flammea nucleopolyhedrovirus (PaflNPV) population, isolated from the pine beauty moth. Variable regions of the PaflNPV genome were sequenced and novel ORFs were identified on each of the enlarged fragments. The roles of these orfs and the implications of their presence or absence within different genotypes are discussed. The variable fragments were also labelled with 32P and used as polymorphic genetic markers of genotype abundance. The proportion of polymorphic loci changed after passage in different insect species and this varied among species, suggesting a role for host selection of pathogen genotypes in the field as a mechanism for maintaining genetic diversity. These results have wide-ranging implications for understanding the ecology of insect-virus interactions in the natural environment and the evolution of baculovirus life history strategies.

Animals↗
PubMed2006

A Survey of the bacteriophage WO in the endosymbiotic bacteria Wolbachia.

Bacteriophages are common viruses infecting prokaryotes. In addition to their deadly effect, phages are also involved in several evolutionary processes of bacteria, such as coding functional proteins potentially beneficial to them, or favoring horizontal gene transfer through transduction. The particular lifestyle of obligatory intracellular bacteria usually protects them from phage infection. However, Wolbachia, an intracellular alpha-proteobacterium, infecting diverse arthropod and nematode species and best known for the reproductive alterations it induces, harbors a phage named WO, which has recently been proven to be lytic. Here, phage infection was checked in 31 Wolbachia strains, which induce 5 different effects in their hosts and infect 25 insect species and 3 nematodes. Only the Wolbachia infecting nematodes and Trichogramma were found devoid of phage infection. All the 25 detected phages were characterized by the DNA sequence of a minor capsid protein gene. Based on all data currently available, phylogenetic analyses show a lack of congruency between Wolbachia or insect and phage WO phylogenies, indicating numerous horizontal transfers of phage among the different Wolbachia strains. The absence of relation between phage phylogeny and the effects induced by Wolbachia suggests that WO is not directly involved in these effects. Implications on phage WO evolution are discussed.

Animals↗
PubMed1998

Genome structure of mycobacteriophage D29: implications for phage evolution.

Mycobacteriophage D29 is a lytic phage that infects both fast and slow-growing mycobacterial species. The complete genome sequence of D29 reveals that it is a close relative of the temperate mycobacteriophage L5, whose sequence has been described previously. The overall organization of the D29 genome is similar to that of L5, although a 3.6 kb deletion removing the repressor gene accounts for the inability of D29 to form lysogens. Comparison of the two genomes shows that they are punctuated by a large number of insertions, deletions, and substitutions of genes, consistent with the genetic mosaicism of lambdoid phages.

Amino Acid Sequence↗
PubMed1992

Anatomy and evolution of proteins displaying the viral capsid jellyroll topology.

In this paper the anatomy of 25 structures containing a jellyroll motif, consisting of eight antiparallel beta-strands forming a so-called beta-barrel, was investigated. This involved performing a careful structural alignment based on hydrogen bonds for the equivalent regions of the tertiary folds and a subsequent analysis of conserved amino acids, equivalenced residue-residue contacts, and various parameters describing the size, shape and other geometrical characteristics of these regions. It was found that the jellyroll motif is best viewed as a two-sheet wedge structure rather than a barrel. The more conserved parameters are discussed. A model of evolutionary development for the jellyroll fold in the various protein and viral structures is proposed.

Amino Acid Sequence↗
PubMed2006

Short-term antiviral activity of TMC278--a novel NNRTI--in treatment-naive HIV-1-infected subjects.

OBJECTIVE: To evaluate antiviral activity, pharmacokinetics, tolerability and safety of TMC278, a non-nucleoside reverse transcriptase inhibitor (NNRTI), when given as a 25, 50, 100 or 150 mg once-daily dose for 7 days to antiretroviral-naive HIV-infected subjects. DESIGN: Randomized, double-blind, placebo-controlled, phase IIa clinical trial. METHODS: Participants were 47 antiretroviral naive HIV-infected subjects. Primary outcome was the change in plasma HIV-1 RNA viral load from baseline to day 8. Secondary outcomes were evaluation of pharmacokinetics of TMC278, immunologic changes, safety and tolerability, and evolution of viral genotypic and phenotypic patterns. RESULTS: Patients treated with TMC278 achieved a median decrease in plasma viral load from baseline of 1.199 log10 copies/ml compared with a 0.002 log10 copies/ml gain in the placebo group (P < 0.01). A significantly higher proportion of subjects in the TMC278 groups obtained a viral load decrease of > 1.0 log10 compared with the placebo group (25/36 versus 0/11) (P < 0.01). No significant dose differences were noted in either antiviral effect or safety. No genotypic changes associated with antiretroviral resistance were detected between baseline and the end of the trial. Plasma concentrations of TMC278 were above the target concentration (13.5 ng/ml) at all time points for all TMC278-treated subjects. The most common reported adverse event was headache (TMC278 14%; placebo 18%). CONCLUSIONS: TMC278 showed antiviral activity when given as monotherapy for 7 days at all doses studied and the drug was safe and well tolerated. Trials of longer treatment duration with TMC278, in combination with other antiretroviral drugs, are underway to assess the long-term durability of antiviral response, safety and tolerability.

Administration, Oral↗