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At least 361 records · Page 20Linked to original sources
PubMed2002

Primary hepatocytes of Tupaia belangeri as a potential model for hepatitis C virus infection.

Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide, but the study of HCV infection has been hampered by the lack of an in vitro or in vivo small animal model. The tree shrew Tupaia belangeri is susceptible to infection with a variety of human viruses in vivo, including hepatitis viruses. We show that primary Tupaia hepatocytes can be infected with serum- or plasma-derived HCV from infected humans, as measured by de novo synthesis of HCV RNA, analysis of viral quasispecies evolution, and detection of viral proteins. Production of infectious virus could be demonstrated by passage to naive hepatocytes. To assess whether viral entry in Tupaia hepatocytes was dependent on the recently isolated HCV E2 binding protein CD81, we identified and characterized Tupaia CD81. Sequence analysis of cloned Tupaia cDNA revealed a high degree of homology between Tupaia and human CD81 large extracellular loops (LEL). Cellular binding of E2 and HCV infection could not be inhibited by anti-CD81 antibodies or soluble CD81-LEL, suggesting that viral entry can occur through receptors other than CD81. Thus, primary Tupaia hepatocytes provide a potential model for the study of HCV infection of hepatocytes.

Animals↗
PubMed1998

Structure, functions, and evolution of the third complement component and viral molecular mimicry.

The third component of the complement system, C3, is a common denominator in the activation of the classical, alternative, and lectin pathways. The ability of C3 molecule to interact with at least 20 different proteins makes it the most versatile component of this system. Since these interactions are important for phagocytic, immunoregulatory, and immune evasion mechanisms, the analysis of its structure and functions has been a subject of intense research. Here we review our current work on the C3-ligand interactions, C3-related viral molecular mimicry, evolution of the complement system, and identification of C3-based complement inhibitors.

Animals↗
PubMed2005

Genetic evolution of HIV in patients remaining on a stable HAART regimen despite insufficient viral suppression.

Our objective was to investigate whether steadily increasing resistance levels are inevitable in the course of a failing but unchanged Highly Active Antiretroviral Therapy (HAART) regimen. Patients having an unchanged HAART regimen and a good CD4 response (100 cells/microl above nadir) despite consistent HIV-RNA levels above 200 copies/ml were included in the study. The study period spanned at least 12 months and included 47 plasma samples from 17 patients that were sequenced and analysed with respect to evolutionary changes. At inclusion, the median CD4 count was 300 cells/ml (inter-quartile range (IQR): 231-380) and the median HIV-RNA was 2000 copies/ml (IQR: 1301-6090). Reverse transcription inhibitor (RTI) mutations increased 0.5 mutations per y (STD = 0.8 mutations per y), while major protease inhibitor (PI) resistance mutations increased at a rate of 0.2 mutations per y (STD = 0.8 mutations per y) and minor PI resistance mutations increased at a rate of 0.3 mutations per y (STD = 0.7 mutations per y). The rate at which RTI mutations accumulated decreased during the study period (p = 0.035). Interestingly, the rate of mutation accumulation was not associated with HIV-RNA level. The majority of patients kept accumulating new resistance mutations. However, 3 out of 17 patients with viral failure were caught in an apparent mutational deadlock, thus the development of additional resistance during a failing HAART is not inevitable. We hypothesize that certain patterns of mutations can cause a mutational deadlock where the evolutionary benefit of further resistance mutation is limited if the patient is kept on a stable HAART regimen.

Adult↗
PubMed1986

Development of specific antibodies mediating antibody-dependent cell-mediated cytotoxicity following experimental infection of cattle with bovine herpesvirus 1 and subsequent viral reactivation.

Evolution of sensitizing antibodies involved in antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-complement cell lysis and complement-facilitated ADCC was followed in bulls after primary infection by a wild strain of infectious bovine rhinotracheitis virus (bovine herpesvirus 1; BHV-1) and after experimental reactivation of the virus. These antibodies were detected between the 4th and the 7th day after primary infection, reached a maximum level after 2 weeks and rose slightly after reactivation of the virus following dexamethasone treatment. The presence of endogenous complement slightly enhanced the ADCC reaction.

Animals↗
PubMedDate not supplied

The application of molecular phylogenetics to the analysis of viral genome diversity and evolution.

DNA sequencing and molecular phylogenetics are increasingly being used in virology laboratories to study the transmission of viruses. By reconstructing the evolutionary history of viral genomes the behaviour of viral populations can be modelled, and the future of epidemics may be forecast. The manner in which such viral DNA sequences are analysed is the focus of this review. Many researchers resort to the often-quoted 'black box' approach because phylogenetics theory can be daunting, and phylogenetics software packages can appear to be difficult to use. However, because phylogenetic analyses are often used in important and sensitive arenas, for example to provide evidence indicating transmission between persons, it is vital that appropriate care is taken to estimate reliably true relationships. In this review, we discuss how a molecular phylogenetics study should be approached, give an overview of the methods and programs for analysing DNA sequence data, and point readers to appropriate texts for further details. The aim of this review, therefore, is to provide researchers with an easy to understand guide to molecular phylogenetics, with special reference to viral genomes.

Amino Acid Sequence↗
PubMed2025

Defective but tumorigenic: the evolutionary and functional roles of mutated oncoviruses.

Human oncogenic viruses contribute significantly to the global health burden and include seven types: Epstein-Barr virus, hepatitis B virus, human T-cell leukemia virus type 1, human papillomavirus, hepatitis C virus, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus. While the roles of latent or integrated viral genomes in cancer have been documented, emerging evidence highlights the contribution of defective viruses-those carrying intragenic deletions or loss-of-function mutations-in promoting viral oncogenesis. These altered genomes often lack genes essential for lytic replication or immune recognition, which enhances their persistence and immune evasion. In virus-associated diseases, specific patterns of gene retention and deletion suggest that host-driven selective pressures drive the emergence of these altered genomes. This review examines the generation, prevalence, and functional impact of these viruses, reframing them as active participants in disease development and progression. Recognizing their role offers new insights into viral tumor evolution and creates opportunities for applications in viral diagnostics and targeted intervention strategies.

Humans↗
PubMed2002

Genetic evolution of structural region of hepatitis C virus in primary infection.

AIM: To investigate the dynamics of hepatitis C virus (HCV) variability through putative envelope genes during primary infection and the mechanism of viral genetic evolution in infected hosts. METHODS: Serial serum samples prospectively collected for 12 to 34 months from a cohort of acutely HCV-infected individuals were obtained, and a 1-kb fragment spanning E1 and the 5' half of E2, including Thirty-three cloned cDNAs representing each specimen were assessed by a method that combined a single-stranded conformational polymorphism (SSCP) and heteroduplex analysis (HDA) method to determine the number of clonotypes hypervariable region, was amplified by reverse transcriptase PCR and cloned. Nonsynonymous mutations per nonsynonymous site (dn), synonymous mutations per synonymous site (ds), dn/ds ratio and genetic distances within each sample were evaluated for intrahost evolutionary analysis. RESULTS: Quasispecies complexity and sequence diversity were lower in early samples and a further increase after seroconversion, although ds value in the envelope genes was higher than dn value during primary infection. The trend, pronounced in most of samples, toward lower ds values in the E1 than in the 5' portion of E2. Quasispecies complexity was higher and E2 dn/ds ratio was a trend toward higher value in later samples during persistent viremia. We also found individual features of HCV genetic evolution in different subjects who were infected with different HCV genotypes. CONCLUSION: Mutations of actively replicating virus arise stochastically with certain functional constaints. A complexity quasispecies exerted by a combination of either neutral evolution or selective forces shows clear differences in individuals, and associated with HCV persistence.

Adult↗
PubMed1994

Intra-host versus inter-host selection: viral strategies of immune function impairment.

We investigate the evolution of viral strategies to counteract immunological attack. These strategies can be divided into two classes: those that impair the immune response inside or at the surface of a virus-infected cell and those that impair the immune response outside an infected cell. The former strategies confer a "selfish" individual selective advantage for intra-host competition among viruses. The latter strategies confer an "unselfish" selective advantage to the virus population as a group. A mutant, defective in the gene coding for the extracellular immune function-impairment strategy, may be protected from immune attack because the wild-type virus in the same host successfully impairs the host's immune function. Such "unselfish" defense strategies are neutral with respect to intra-host competition. We present simple models of viral intra-host and combined inter- and intra-host evolution. We show that selfish strategies can evolve by intra-host evolution. Unselfish strategies may evolve if inter-host selection pressures outweigh intra-host selection, suggesting that such strategies can only evolve in viruses with low mutation rates.

Animals↗
PubMed1975

Evolution of type C viral genes: preservation of ancestral murine type C viral sequences in pig cellular DNA.

Domestic pigs (Sus scrofa) and other members of the family Suidae have multiple copies of type C viral gene sequences in the cellular DNA of all their tissues. Partially homologous viral gene sequences are also found in cellular DNA of rodents, particularly Muridae. The results lead to the conclusion that type C viral genes were introduced into the Suidae lineage as a result of trans-species infection by an ancestral xenotropic murine virus. The rate of evolution of the virogene sequences in the pig appears to be much slower than that of genes that have remained in the rodent lineage; this may be a consequence of transfer from a shorter-lived animal (the rodent) to a longer-lived one (the pig). We estimate the time of gene transmission as 5-10 million years ago and conclude that the present-day porcine type C virogenes most closely approximate the viral genes as they were several million years ago in the rodent lineage.

Animals↗
PubMed2006

Phylogenetic evidence for the rapid evolution of human B19 erythrovirus.

Human B19 erythrovirus is a ubiquitous viral pathogen, commonly infecting individuals before adulthood. As with all autonomous parvoviruses, its small single-stranded DNA genome is replicated with host cell machinery. While the mechanism of parvovirus genome replication has been studied in detail, the rate at which B19 virus evolves is unknown. By inferring the phylogenetic history and evolutionary dynamics of temporally sampled B19 sequences, we observed a surprisingly high rate of evolutionary change, at approximately 10(-4) nucleotide substitutions per site per year. This rate is more typical of RNA viruses and suggests that high mutation rates are characteristic of the Parvoviridae.

Base Sequence↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2001

Detection of homologous recombination among bacteriophage P2 relatives.

Sequencing of five late genes from 18 isolates of P2-like bacteriophages showed that these are at least 96% identical to the genes of phage P2. A maximum-parsimony phylogenetic analysis of these genes showed excess homoplasy of a magnitude three to six times higher than that expected. Examination of the distribution of the number of homoplasies at parsimoniously informative sites and incompatibility matrices of such sites revealed a pattern typical for extensive recombination. It has been shown that phage P2 probably incorporated some functionally complete genes or gene modules by recombination with other phages or with different hosts, but homologous recombination within genes has previously not been shown. In this paper we demonstrate that homologous recombination between P2-like bacteriophages occurs randomly at multiple breakpoints in five late genes. The rate of recombination is high but, since some phages were sampled decades apart and in different parts of the world, this has to be viewed on an evolutionary time scale. The applicability of different methods used for detection of recombination breakpoints and estimation of rates of recombination in bacteriophages is discussed.

Bacteriophage P2↗
PubMed1999

The genome nucleotide sequence of a contemporary wild strain of measles virus and its comparison with the classical Edmonston strain genome.

The only complete genome nucleotide sequences of measles virus (MeV) reported to date have been for the Edmonston (Ed) strain and derivatives, which were isolated decades ago, passaged extensively under laboratory conditions, and appeared to be nonpathogenic. Partial sequencing of many other strains has identified >/=15 genotypes. Most recent isolates, including those typically pathogenic, belong to genotypes distinct from the Edmonston type. Therefore, the sequence of Ed and related strains may not be representative of those of pathological measles circulating at that or any time in human populations. Taking into account these issues as well as the fact that so many studies have been based upon Ed-related strains, we have sequenced the entire genome of a recently isolated pathogenic strain, 9301B. Between this recent isolate and the classical Ed strain, there were 465 nucleotide differences (2.93%) and 114 amino acid differences (2.19%). Computation of nonsynonymous and synonymous substitutions in open reading frames as well as direct comparisons of noncoding regions of each gene and extracistronic regulatory regions clearly revealed the regions where changes have been permissible and nonpermissible. Notably, considerable nonsynonymous substitutions appeared to be permissible for the P frame to maintain a high degree of sequence conservation for the overlapping C frame. However, the cause and the effect were largely unclear for any substitution, indicating that there is a considerable gap between the two strains that cannot be filled. The sequence reported here would be useful as a reference of contemporary wild-type MeV.

3' Untranslated Regions↗
PubMed2001

The complete DNA sequence of the Ectocarpus siliculosus Virus EsV-1 genome.

The Ectocarpus siliculosus Virus-1, EsV-1, is the type-species of a genus of Phycodnaviridae, the phaeoviruses, infecting marine filamentous brown algae. The EsV-1 genome of 335,593 bp contains tandem and dispersed repetitive elements in addition to a large number of open reading frames of which 231 are currently counted as genes. Many genes can be assigned to functional groups involved in DNA synthesis, DNA integration, transposition, and polysaccharide metabolism. Furthermore, EsV-1 contains components of a surprisingly complex signal transduction system with six different hybrid histidine protein kinases and four putative serine/threonine protein kinases. Several other genes encode polypeptides with protein-protein interaction domains. However, 50% of the predicted genes have no counterparts in data banks. Only 28 of the 231 identified genes have significant sequence similarities to genes of the Chlorella virus PBCV-1, another phycodnavirus. To our knowledge, the EsV-1 genome is the largest viral DNA sequenced to date.

Amino Acid Sequence↗
PubMed1996

The complete nucleotide sequence and genome organization of barley mild mosaic virus (Na1 strain).

The 5'-terminal half of RNA 1 and whole of RNA 2 of barley mild mosaic bymovirus Na1 strain (BaMMV-Na1) were sequenced to give together with the published data its complete genomic sequence. BaMMV-Na1 RNA 1 and RNA 2 consist of 7263 and 3516 nucleotides, excluding the 3' poly A tails, respectively. RNA 1 encodes a single large polyprotein of 2258 amino acids (M(r) 256K), containing eight putative functional proteins, and RNA 2 also encodes one polyprotein of 891 amino acids (M(r) 98K), containing two functional proteins. These functional proteins are arranged in the same manner as in RNA 1 and RNA 2 of barley yellow mosaic bymovirus (BaYMV), and significant amino acid sequence homology (25-58%) exists between the proteins of the two viruses. The BaMMV-Na1 proteins show less amino acid sequence homology (18-32%) with the corresponding proteins of potyviruses or rymoviruses than with those of BaYMV. Comparisons of the BaMMV-Na1 proteins with the corresponding proteins of other partially sequenced BaMMV isolates show 87-98% amino acid sequence identity. There is 91-94% nucleotide sequence identity between the 3' non-coding regions (NCRs) in RNA 1 or RNA 2 of BaMMV-Na1 and other BaMMV isolates, but only 68-72% identity between the 5' NCRs in RNA 2 of BaMMV-Na1 and other BaMMV isolates.

Amino Acid Sequence↗
PubMed1999

Evolutionary pattern of influenza B viruses based on the HA and NS genes during 1940 to 1999: origin of the NS genes after 1997.

Phylogenetic analysis was carried out for genes encoding hemagglutinin (HA) (24 new and 25 previously reported sequences) and nonstructural proteins (NS) (22 new and 14 previously reported sequences) of influenza B virus isolates obtained from 1940 to 1999. Two antigenically and genetically distinct HA lineages are presently known to exist. Divergence into these two lineages was estimated to have occurred around 1969. Phylogenetic analysis of NS genes revealed that their phylogenetic relationships were not linked to the two HA lineages but suggested that reassortment of viral genes between the viruses of two HA lineages had occurred. In addition two distinct NS lineages which were not linked to the two HA lineages were observed. Viruses isolated after 1997 formed their own lineage in combination with B/Houston/84 while other virus isolates obtained from 1973 to 1995 comprised the other NS lineage.

Base Sequence↗