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At least 811 records · Page 45Linked to original sources
PubMed2005

Natural evolution of a human virus-specific antibody gene repertoire by somatic hypermutation requires both hotspot-directed and randomly-directed processes.

Somatic hypermutation of antibody genes is mediated by activation-induced cytidine deaminase and targets primarily hotspot motifs. We tested the hypothesis that the antibody variable genes of virus-specific B cells from infants exhibit a decreased frequency of somatic mutations compared with adults. We also sought to determine whether virus-specific B cells exhibit predominantly hotspot or randomly directed processes. We analyzed somatic mutations in rotavirus (RV)-specific B cells from otherwise healthy but recently RV-infected infants or adults in comparison with B cells from healthy volunteers not recently infected. We compared these antibody variable gene sequences with those derived from RV-specific B cells from an adult patient with X-linked hyper-IgM syndrome (XHIM). We found that the overall mutational frequency within the antibody variable region was lowest in RV-specific B cells from RV-infected infants, followed by randomly selected B cells, followed by RV-specific B cells from the patient with XHIM. RV-specific memory B cells from healthy adults exhibited the highest frequency of mutations. Approximately half of mutations in random or RV-specific B cells from adults or infants occurred at the DGYW/WRCH or WA/TW hotspot motifs. These findings suggest that virus-specific antibodies require both hotspot and randomly-directed processes.

Adult↗
PubMed1999

Possible emergence of new geminiviruses by frequent recombination.

Although exchange of genetic information by recombination plays a role in the evolution of viruses, the extent to which it generates diversity is not clear. We analyzed genomes of geminiviruses for recombination using a new statistical procedure developed to detect gene conversions. Geminiviruses (family, Geminiviridae) are a group of plant viruses characterized by a genome of circular single-stranded DNA (approximately 2700 nucleotides in length) encapsidated in twinned quasi-isometric particles. Complete nucleotide sequences of geminiviruses were aligned, and recombination events were detected by searching pairs of viruses for sequences that are significantly more similar than expected based on random distribution of polymorphic sites. The analyses revealed that recombination is very frequent and occurs between species and within and across genera. Tests identified 420 statistically significant recombinant fragments distributed across the genome. The results suggest that recombination is a significant contributor to geminivirus evolution. The high rate of recombination may be contributing to the recent emergence of new geminivirus diseases.

Evolution, Molecular↗
PubMed2000

Defining CTL-induced pathology: implications for HIV.

The relationship between virus and host cells is multifactorial and nonlinear. This indicates that the effect of an immune response on infection can lead to several different outcomes. These include severe immunopathology. We seek to define properties of CTL-induced pathology in viral infections and examine the implications for HIV disease progression. We find that CTL-induced pathology is observed if the rate of viral replication is fast relative to the CTL responsiveness of the host. Theoretical predictions are consistent with empirical data on LCMV infection. These conditions are also sufficient to induce pathology in HIV infection. However, the absence of HIV-specific CTL can result in an equivalent depletion of the CD4 T cell pool as a consequence of the short life span of activated T cells. A mathematical model describing the evolution of HIV coreceptor usage in the context of lytic and nonlytic CD8 cell responses might account for the relatively long time span required to result in disease. Viral evolution toward parameter ranges allowing CTL-induced pathology is difficult to achieve. It requires the emergence of fast viral replication together with escape from nonlytic CTL responses. However, according to the model, fast viral replication can result in the evolution of virus strains that are susceptible to chemokine-mediated inhibition of viral replication.

Biological Evolution↗
PubMed2000

Estimating the rate of molecular evolution: incorporating non-contemporaneous sequences into maximum likelihood phylogenies.

MOTIVATION: TipDate is a program that will use sequences that have been isolated at different dates to estimate their rate of molecular evolution. The program provides a maximum likelihood estimate of the rate and also the associated date of the most recent common ancestor of the sequences, under a model which assumes a constant rate of substitution (molecular clock) but which accommodates the dates of isolation. Confidence intervals for these parameters are also estimated. RESULTS: The approach was applied to a sample of 17 dengue virus serotype 4 sequences, isolated at dates ranging from 1956 to 1994. The rate of substitution for this serotype was estimated to be 7.91 x 10(-4) substitutions per site per year (95% confidence intervals of 6.07 x 10(-4), 9.86 x 10(-4)). This is compatible with a date of 1922 (95% confidence intervals of 1900-1936) for the most recent common ancestor of these sequences. AVAILABILITY: TipDate can be obtained by WWW from http://evolve.zoo. ox.ac.uk/software. The package includes the source code, manual and example files. Both UNIX and Apple Macintosh versions are available from the same site.

DNA, Viral↗
PubMed2004

Changes in in vitro susceptibility of influenza A H3N2 viruses to a neuraminidase inhibitor drug during evolution in the human host.

OBJECTIVES: Influenza A H3N2 viruses isolated recently have characteristic receptor binding properties that may decrease susceptibility to neuraminidase inhibitor drugs. A panel of clinical isolates and recombinant viruses generated by reverse genetics were characterized and tested for susceptibility to zanamivir. METHODS: Plaque reduction assays and neuraminidase enzyme inhibition assays were used to assess susceptibility to zanamivir. Receptor binding properties of the viruses were characterized by differential agglutination of red blood cells (RBCs) from different species. Sequence analysis of the haemagglutinin (HA) and neuraminidase (NA) genes was carried out. RESULTS: Characterization of a panel of H3N2 clinical isolates from 1968 to 2000 showed a gradual decrease in agglutination of chicken and guinea pig RBCs over time, although all isolates could agglutinate turkey RBCs equally. Sequence analysis of the HA and NA genes identified mutations in conserved residues of the HA1 receptor binding site, in particular Leu-226 --> Ile-226/Val-226, and modification of potential glycosylation site motifs. This may be indicative of changes in virus binding to sialic acid (SA) receptors in recent years. Although recent isolates had reduced susceptibility to zanamivir in MDCK cell based plaque reduction assays, no difference was found in an NA enzyme-inhibition assay. Assays with recombinant isogenic viruses showed that the recent HA, but not the NA, conferred reduced susceptibility to zanamivir. CONCLUSION: This study demonstrates that recent clinical isolates of influenza A H3N2 virus no longer agglutinate chicken RBCs, but despite significant receptor binding changes as a result of changes in HA, there was little variation in sensitivity of the NA to zanamivir.

Animals↗
PubMed1977

Virus-like particles in Ustilago maydis: mutants with partial genomes.

Mutants with partial genomes for the virus-like particles of U. maydis were recovered following treatment with nitrosoguanidine. Examination of the properties retained by progeny of genetic crosses indicates that the 2.9 X 10(6) dalton component of double-stranded RNA contains the information for capsid formation and dsRNA replication. Other components appear to contain the information for killer function and immunity to killer. The use of such mutants for studies on the evolution of viruses with segmented genomes is discussed.

Basidiomycota↗
PubMed1976

Pathology of influenza hepatitis in susceptible and genetically resistant mice.

Mice resistant (homozygous or heterozygous for the gene Mx) and mice susceptible to the lethal effect of influenza viruses were inoculated intraperitoneally and intraportally with a hepatotropic variant of influenza A virus. Disease evolution was followed histologically and by immunofluorescence. In susceptible animals, rapidly spreading foci of hepatocyte necrosis with little inflammatory infiltration was observed. Death occurred on the 3rd day, when the entire liver was involved. In resistant animals foci became detectable later, and were fewer and smaller. They were infiltrated by cells morphologically resembling liver macrophages (Kupffer cells), and they regressed from the 4th day after infection. Barriers to virus spread appeared to be present at all stages of the disease.

Animals↗
PubMed1997

Molecular variation, evolution and geographical distribution of louping ill virus.

Following the demonstration that the tick-borne encephalitis (TBE) subgroup viruses are distributed as a cline across the Northern Hemisphere (Zanotto et al., 1995), we have analyzed the dispersal pattern of louping ill (LI) virus, the most westerly located member in the cline. A total number of 21 LI or LI-related virus E gene sequences have been used for a detailed molecular analysis of the evolution, phylogeny and geographical distribution of LI virus in the British Isles and Ireland. The results show that LI virus is genetically stable in general but minor differences enable its separation into four genetically distinct subtypes (genotypes) with clear geographical correlation, designated Type 1 in Scotland and England, Type 2 in Scotland, Type 3 in Wales and Type 4 in Ireland. These data demonstrate that geographically independent evolution of LI viruses has occurred. The molecular systematics and substitutional parameters analyses combined with the clinal distribution of the TBE virus complex allow the assignment of the origin for both Negishi (NEG) virus and a Norwegian isolate to the British Isles. Moreover, proposals for the classification of LI and LI-like viruses which cause encephalomyelitis in sheep, goat or cattle are presented.

Animals↗
PubMed2001

Multiplicity of infection and the evolution of hybrid incompatibility in segmented viruses.

Some viral genomes are divided into segments. When multiple viruses infect a single cell, progeny form by reassorted mixtures of genomic segments. Hybrid incompatibilities arise when a progeny virus has incompatible segments from different parental viruses. Hybrid incompatibility has been observed in influenza and in the multiparticle plant virus Dianthovirus. Hybrid incompatibility provides an opportunity to study rates of viral evolution, divergence and speciation, and the extent of epistatic interactions among components of the viral genome. This paper presents mathematical and computer simulation models to study hybrid incompatibility between diverging strains. The models identify multiplicity of infection as a key factor. When many viral particles infect each host cell, the effective ploidy of the genetic system is high. High ploidy dilutes the contribution of each locus to the phenotype, weakening the selective intensity on each locus. Weaker selection on variant alleles allows the population to maintain greater genetic diversity and to be more easily perturbed by stochastic fluctuations. Greater diversity and stochastic fluctuations explore more widely the space of epistatic interactions, causing more frequent shifts among favoured combinations of alleles. Variable ploidy of viral genetics differs from standard Mendelian genetics.

Computer Simulation↗
PubMed2006

Reassortment and concerted evolution in banana bunchy top virus genomes.

The nanovirus Banana bunchy top virus (BBTV) has six standard components in its genome and occasionally contains components encoding additional Rep (replication initiation protein) genes. Phylogenetic network analysis of coding sequences of DNA 1 and 3 confirmed the two major groups of BBTV, a Pacific and an Asian group, but show evidence of web-like phylogenies for some genes. Phylogenetic analysis of 102 major common regions (CR-Ms) from all six components showed a possible concerted evolution within the Pacific group, which is likely due to recombination in this region. The CR-M of additional Rep genes is close to that of DNA 1 and 2. Comparison of tree topologies constructed with DNA 1 and DNA 3 coding sequences of 14 BBTV isolates showed distinct phylogenetic histories based on Kishino-Hasegawa and Shimodaira-Hasegawa tests. The results of principal component analysis of amino acid and codon usages indicate that DNA 1 and 3 have a codon bias different from that of all other genes of nanoviruses, including all currently known additional Rep genes of BBTV, which suggests a possible ancient genome reassortment event between distinctive nanoviruses.

Asia↗
PubMed2003

Pathogenesis of human immunodeficiency virus-induced neurological disease.

Infection of the central nervous system by the type 1 human immunodeficiency virus (HIV-1) commonly results in a number of neurological impairments known, in their most severe form, as HIV-associated dementia (HAD). The persistence of HIV encephalitis (HIVE), the pathological correlate of HAD, in spite of highly active antiretroviral therapy (HAART) underscores the importance of continued research focused on the neurobiology of HIV. To elucidate direct and indirect mechanisms of HIV neuropathogenesis, current investigation is focused on neuroinvasion, HIV-1-mediated mechanisms of neuronal damage and apoptosis, and compartmentalized evolution of virus in the brain. The aim of this review is to provide a selective overview of the most recent research on the neurobiology of HIV, adding only a brief introduction regarding established principles.

AIDS Dementia Complex↗
PubMed2004

Comparative study of adaptive molecular evolution in different human immunodeficiency virus groups and subtypes.

Molecular adaptation, as characterized by the detection of positive selection, was quantified in a number of genes from different human immunodeficiency virus type 1 (HIV-1) group M subtypes, group O, and an HIV-2 subtype using the codon-based maximum-likelihood method of Yang and coworkers (Z. H. Yang, R. Nielsen, N. Goldman, and A. M. K. Pedersen, Genetics 155:431-449, 2000). The env gene was investigated further since it exhibited the strongest signal for positive selection compared to those of the other two major HIV genes (gag and pol). In order to investigate the pattern of adaptive evolution across env, the location and strength of positive selection in different HIV-1 sequence alignments was compared. The number of sites having a significant probability of being positively selected varied among these different alignment data sets, ranging from 25 in HIV-1 group M subtype A to 40 in HIV-1 group O. Strikingly, there was a significant tendency for positively selected sites to be located at the same position in different HIV-1 alignments, ranging from 10 to 16 shared sites for the group M intersubtype comparisons and from 6 to 8 for the group O to M comparisons, suggesting that all HIV-1 variants are subject to similar selective forces. As the host immune response is believed to be the dominant driving force of adaptive evolution in HIV, this result would suggest that the same sites are contributing to viral persistence in diverse HIV infections. Thus, the positions of the positively selected sites were investigated in reference to the inferred locations of different epitope types (antibody, T helper, and cytotoxic T lymphocytes) and the positions of N and O glycosylation sites. We found a significant tendency for positively selected sites to fall outside T-helper epitopes and for positively selected sites to be strongly associated with N glycosylation sites.

Adaptation, Physiological↗
PubMed2000

Analysis of env sequence evolution in human immunodeficiency virus-infected patients receiving therapy with nonnucleoside reverse-transcriptase inhibitors.

Nonnucleoside reverse-transcriptase inhibitors (NNRTIs) can rapidly select for drug-resistant human immunodeficiency virus type 1 (HIV-1) variants, although their effect on HIV-1 quasi-species diversity is unknown. To determine if changes in env gene diversification occur with NNRTI therapy, we used the heteroduplex tracking assay (HTA) to study HIV-1 env sequence diversity in 2 groups of patients: those who were on no therapy or were on chronic antiretroviral therapy and those who had just initiated NNRTIs. Forty-nine paired samples from 46 patients were analyzed. Fourteen of 32 paired samples from the NNRTI group and 9 of 17 paired samples from the control group had HTA changes (P>.10). There was no correlation between HTA change and sampling time interval, baseline virus load, change in virus load, or development of NNRTI resistance. Thus, we found no significant correlation of NNRTI therapy with changes in env HTA patterns, suggesting that these treatments had little short-term impact on HIV-1 quasi-species diversity.

Drug Resistance, Microbial↗
PubMed2001

Phylogenetic and evolutionary relationships among yellow fever virus isolates in Africa.

Previous studies with a limited number of strains have indicated that there are two genotypes of yellow fever (YF) virus in Africa, one in west Africa and the other in east and central Africa. We have examined the prM/M and a portion of the E protein for a panel of 38 wild strains of YF virus from Africa representing different countries and times of isolation. Examination of the strains revealed a more complex genetic relationship than previously reported. Overall, nucleotide substitutions varied from 0 to 25.8% and amino acid substitutions varied from 0 to 9.1%. Phylogenetic analysis using parsimony and neighbor-joining algorithms identified five distinct genotypes: central/east Africa, east Africa, Angola, west Africa I, and west Africa II. Extensive variation within genotypes was observed. Members of west African genotype II and central/east African genotype differed by 2.8% or less, while west Africa genotype I varied up to 6.8% at the nucleotide level. We speculate that the former two genotypes exist in enzootic transmission cycles, while the latter is genetically more heterogeneous due to regular human epidemics. The nucleotide sequence of the Angola genotype diverged from the others by 15.7 to 23.0% but only 0.4 to 5.6% at the amino acid level, suggesting that this genotype most likely diverged from a progenitor YF virus in east/central Africa many years ago, prior to the separation of the other east/central African strains analyzed in this study, and has evolved independently. These data demonstrate that there are multiple genotypes of YF virus in Africa and suggest independent evolution of YF virus in different areas of Africa.

Africa↗
PubMed1990

[Acute viral hepatitis in children].

In children with acute hepatitis the main concern is to identify the cause since prognosis and therefore management largely depend on the specific causative agent. Since HAV is the most frequent in children, it should be investigated first. If there are no IGM anti-HAV antibodies, hepatitis B should be investigated. The value of anti-HCV antibodies, during acute hepatitis is not clear. Whatever the virus, severe evolution may occur, and symptoms of poor significance must be detected early. There is no risk of chronic evolution for hepatitis A. Follow-up studies of patients with hepatitis B should be performed to ensure clearance of HBSAg or to recognize the development of a chronic carrier state. Preventive measures include a search for a chronic carrier in the family and vaccination of the negative sibling or parents. In infancy, the diagnosis of "neonatal hepatitis" must be asserted by the presence of serological markers of viral infection. In the absence of such markers, other causes of cholestasis in infancy must be investigated. Perinatal transmission of hepatitis B virus should be now prevented by screening for women from high-risk groups and administration of immunoglobulins and vaccine to the neonates.

Acute Disease↗
PubMed1996

Evolution in a chronic RNA virus infection: selection on HTLV-I tax protein differs between healthy carriers and patients with tropical spastic paraparesis.

HTLV-I causes T-cell leukemia and tropical spastic paraparesis (TSP) in a minority of infected people, whereas the majority remain healthy. The virus differs little in sequence between isolates but has been shown to have a quasispecies structure. Using the Nei and Gojobori algorithm, we have shown that the proportion of nonsynonymous to synonymous changes in HTLV-I proviral tax gene sequences from healthy seropositive subjects (Dn/Ds = 0.9 to 1.3) is significantly higher than those from TSP patients (Dn/Ds = 0.3 to 0.6). Here we show that the distinction between healthy seropositives and TSP patients can only be seen with proviral tax sequences, but not with cDNA, the amino-terminal or carboxy-terminal half of tax, or the rex gene. The Dn/Ds ratio of proviral tax sequences was used to analyze two TSP patients with atypical features and to investigate the influence of cytotoxic T cells (CTL) on the viral quasispecies.

Biological Evolution↗
PubMed1994

Protein-protein interactions and glycerophospholipids in bromovirus and nodavirus RNA replication.

The plant bromoviruses and animal nodaviruses are distinct groups of positive strand RNA viruses that have proven to be useful models for RNA replication studies. Bromoviruses encode two large proteins required for RNA replication: 1a contains domains implicated in helicase and capping functions, and 2a contains a central polymerase-like domain. Using immunoprecipitation and far-western blotting, we have now shown that 1a and 2a form a specific complex in vitro and have mapped the interacting domains. Molecular genetic data implicate the 1a-2a complex in RNA replication and suggest that it supports coordinate action of the putative helicase, polymerase, and capping domains. The locations of the interacting 1a and 2a domains have implications for replication models and the evolution of virus genomes bearing homologous replication genes in fused vs. divided forms. For the nodavirus Flock house virus (FHV), a true RNA replicase has been isolated that carries out complete, highly active replication of added FHV RNA, producing newly synthesized positive strand RNA in predominantly ssRNA form. Positive strand RNA synthesis in this FHV cell-free system is strongly dependent on the addition of any of several glycerophospholipids. Positive strand RNA synthesis depends on the complete glycerophospholipid structure, including the polar head group and diacyl glycerol lipid portion, and is strongly influenced by acyl chain length.

Bromovirus↗