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At least 451 records · Page 25Linked to original sources
PubMed2001

A new algorithm for analysis of within-host HIV-1 evolution.

A new algorithm for inferring the evolution of within-host viral sequences is presented. A sequential-linking approach is developed so that a longitudinal phylogenetic tree can be reconstructed from sequential molecular data that are obtained at different time points from the same host. The algorithm employs a codon-based model, which uses a Markov process to describe substitutions between codons, to calculate nonsynonymous and synonymous substitution rates and to distinguish positive selection and neutral evolution. The algorithm is applied to a data set of the V3 region of the HIV-1 envelope genes sequenced at different years after the infection of a single patient. The results suggest that this algorithm may provide a more realistic description of viral evolution than traditional evolutionary models, because it accounts for both neutral and adaptive evolution, and reconstructs a longitudinal phylogenetic tree that describes the dynamic process of viral evolution.

Algorithms↗
PubMed2001

Hepatitis C virus. The importance of viral heterogeneity.

Although recent evidence indicates that the quasispecies nature of HCV constitutes a critical strategy for the virus to survive in the host, the mechanisms of viral persistence remain unknown. Similarly, the correlates of immune protection in a limited proportion of individuals who succeed in clearing HCV are still largely undefined. Understanding the mechanisms of sterilizing immunity is essential for devising preventive measures against HCV and unraveling how the virus eludes such immunity. As in other viral infections, the complex interactions between the virus and the host early in the course of HCV infection probably determine the outcome of the disease (i.e., resolution or persistence). The evidence now accumulated on HCV and other models of viral infection is compatible with the hypothesis that both cellular and humoral components are needed for definitive viral clearance. Nevertheless, detailed studies of the specific cellular and humoral immune responses during the incubation period and the acute phase of hepatitis C, in relation to the viral quasispecies evolution and the clinical outcome, are still lacking both in humans and in the chimpanzee model. Until such studies are performed, most ideas of viral clearance mechanisms remain hypothetical, and the immunologic basis of HCV clearance will continue to be inferred from associations rather than from causal relationships.

Acute Disease↗
PubMed2006

Long-term evolution of serum and liver viral markers in patients treated for chronic hepatitis C and sustained response.

Few studies have analysed the evolution of HCV markers in chronic hepatitis C (CHC)-treated patients. We have evaluated the presence or absence of serum and liver HCV-RNA, the core antigen (HCV-cAg) and the loss of specific antibodies (anti-HCV), in long-term sustained responders (SR). One hundred and seventy-six patients (132 SR and 44 nonresponders (NR) were included in the study. HCV-RNA was determined in serum and liver by a commercial PCR-kit. HCV-Ag was determined by ELISA and specific antibodies against HCV by means of a commercial line immunoblot assay (LIA) technique. Serum HCVcAg was found positive in three (4.2%) SR and in one (4%) NR (NS). Four SR (3.6%) and 44 NR (100%) were also HCV-RNA (+) in liver tissue. Two patients were HCV-cAg (+). A good correlation was found between the serum levels of HCV-cAg and HCV-RNA (r = 0.847, P < 0.001). Specific antibodies (anti-HCV) were determined by LIA in 45 patients. A decrease was found in the number of patients who presented reactivity to bands E2 and NS4 when we compared SR with a follow-up of more than 5 years with NR and SR with a follow-up <5 years (P < 0.01 and 0.005). A good correlation was found between the HCV-cAg and HCV-RNA serum levels in CHC-treated patients (P < 0.001). Few SR (3.6%) had HCV-RNA in the liver, and HCV-cAg (1.8%) in serum. In SR with more than 5 years of follow-up a clear tendency exists in the trend to clarify the bands E2 and NS4 of anti-HCV in serum.

Adult↗
PubMedDate not supplied

Rapid full-length genomic sequencing of two cytopathically heterogeneous Australian primary HIV-1 isolates.

Two Australian HIV-1 isolates, derived from patient blood (HIV(MBC200)) and cerebrospinal fluid (HIV(MBC925)), were characterized after in vitro culture in peripheral blood mononuclear cells (PBMC). Although virus replication was similar, as measured by cell-free reverse transcriptase activity, only one of the two isolates (HIV-1(MCB200)) consistently induced cell syncytia and depleted the PBMC population of CD4+ cells by cell killing. A novel technique, devised for rapidly obtaining high-quality viral sequence data and the full-length genomic sequence of these two isolates, is presented. Analysis of the predicted sequence of the viral Env proteins provides correlates of the observed phenotypes. Phylogenetic analysis derived using near full-length sequence of these and other HIV-1 subtype B genomic sequences (including two other Australian isolates) shows a star-shaped phylogeny with each member having a similar genetic diversity. These data expand the database of genomic sequence available from well-characterized primary clinical isolates of HIV-1 using a novel rapid technique.

Acquired Immunodeficiency Syndrome↗
PubMed2006

A combined empirical and mechanistic codon model.

The evolutionary selection forces acting on a protein are commonly inferred using evolutionary codon models by contrasting the rate of synonymous to nonsynonymous substitutions. Most widely used models are based on theoretical assumptions and ignore the empirical observation that distinct amino acids differ in their replacement rates. In this paper, we develop a general method that allows assimilation of empirical amino acid replacement probabilities into a codon-substitution matrix. In this way, the resulting codon model takes into account not only the transition-transversion bias and the nonsynonymous/synonymous ratio, but also the different amino acid replacement probabilities as specified in empirical amino acid matrices. Different empirical amino acid replacement matrices, such as secondary structure-specific matrices or organelle-specific matrices (e.g., mitochondria and chloroplasts), can be incorporated into the model, making it context dependent. Using a diverse set of coding DNA sequences, we show that the novel model better fits biological data as compared with either mechanistic or empirical codon models. Using the suggested model, we further analyze human immunodeficiency virus type 1 protease sequences obtained from drug-treated patients and reveal positive selection in sites that are known to confer drug resistance to the virus.

Amino Acid Substitution↗
PubMed2026

Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion.

Viruses are intracellular parasites that reprogram the host proteome to promote replication and evade immune recognition. We applied a virome-wide library of ~10,000 open reading frames to discover viral ubiquitin ligases, mapping their mechanisms of degradation and host substrates using targeted CRISPR screens and proteomics. These viral effectors could be classified as canonical ligases that mimic host E3s, hijackers that redirect host E3s, and noncanonical ligases that rewire cullin-RING ligase machinery. These diverse strategies of virus-mediated degradation converged on immune-related substrates, including JAK1 and CUL1&#x3b2;-TrCP, underscoring immune evasion as a major driver of viral ubiquitin ligase evolution. Our findings elucidate viral strategies for exploiting the ubiquitin-proteasome system with potential for therapeutic targeting.

Humans↗
PubMed1999

Quasispecies of TT virus (TTV) with sequence divergence in hypervariable regions of the capsid protein in chronic TTV infection.

Three hypervariable regions were identified in a central portion of open reading frame 1 of TT virus DNA, which codes for a putative capsid protein of 770 amino acids. TT virus circulates as quasispecies, with many amino acid substitutions in hypervariable regions, to evade immune surveillance of the hosts and to establish a persistent infection.

Acute Disease↗
PubMed1997

Human immunodeficiency virus type 1 genetic evolution in children with different rates of development of disease.

The rate of development of disease varies considerably among human immunodeficiency virus type 1 (HIV-1)-infected children. The reasons for these observed differences are not clearly understood but most probably depend on the dynamic interplay between the HIV-1 quasispecies virus population and the immune constraints imposed by the host. To study the relationship between disease progression and genetic diversity, we analyzed the evolution of viral sequences within six perinatally infected children by examining proviral sequences spanning the C2 through V5 regions of the viral envelope gene by PCR of blood samples obtained at sequential visits. PCR product DNAs from four sample time points per child were cloned, and 10 to 13 clones from each sample were sequenced. Greater genetic distances relative to the time of infection were found for children with low virion-associated RNA burdens and slow progression to disease relative to those found for children with high virion-associated RNA burdens and rapid progression to disease. The greater branch lengths observed in the phylogenetic reconstructions correlated with a higher accumulation rate of nonsynonymous base substitutions per potential nonsynonymous site, consistent with positive selection for change rather than a difference in replication kinetics. Viral sequences from children with slow progression to disease also showed a tendency to form clusters that associated with different sampling times. These progressive shifts in the viral population were not found in viral sequences from children with rapid progression to disease. Therefore, despite the HIV-1 quasispecies being a diverse, rapidly evolving, and competing population of genetic variants, different rates of genetic evolution could be found under different selective constraints. These data suggest that the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations are compatible with a Darwinian system evolving under the constraints of natural selection.

Amino Acid Sequence↗
PubMed2006

Effects of monotherapy with (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) on the evolution of a primary Simian immunodeficiency virus (SIV) isolate.

Determining the impact of antiretroviral therapy on virus evolution could advance the development of improved therapeutics/vaccines against HIV. Toward this goal, we analyzed virus burden, quasispecies complexity, and T cell responses in SIV/DeltaB670-infected rhesus macaques+/-treatment for 7 months with PMPA (2-30 weeks postinfection). Treatment divided the animals into two groups: poor responders (a reduction of < or =1 log) and responders (> or =2 log reduction) in virus burden. Virus evolution in poor responders and untreated controls was characterized by expression of a complex quasispecies that evolved as the disease progressed. This included the universal loss of a viral genotype selected against by in vitro passage in monkey cells and selected for by propagation in human cells. In contrast, a good response to PMPA was characterized by infection with a less complex quasispecies that evolved more slowly. Interestingly, in 2 of the best responders, the human-preferred genotype persisted until the study was discontinued (89 weeks p.i.). Neither virus burden nor the magnitude of the T cell response at 2 weeks postinfection predicted PMPA responsiveness. However, responders expressed a less complex quasispecies than nonresponders prior to treatment. These data suggest a role for intrinsic host factors in treatment responsiveness, and lend support for therapeutic vaccination as an adjunct to effective therapy.

Adenine↗
PubMed1998

Phylogenetic analysis of triple gene block viruses based on the TGB 1 homolog gene indicates a convergent evolution.

The complete nucleotide sequence of the triple gene block one (TGB 1) of cymbidium mosaic potexvirus (CymMV) was compared to those from other potex-, carla-, furo- and hordeiviruses. Seven conserved motifs in the TGB 1, including the ATP-GTP binding domain (P-Loop) consensus GXXGKTSTS, were found in all four virus genera. We propose that all TGBV can be classified into phylogenetic clusters based on their TGB 1 homolog genes. These clusters can be further delineated to form subgroups. The first cluster comprises the potexviruses which are further subdivided into three subgroups; BaMV, FMV, PlaMV and PapMV (subgroup Ia); CymMV, PAMV, NMV, SMYEaV and WC1MV (subgroup Ib) and PVX (subgroup Ic). The second cluster comprises carlaviruses with a dual subgrouping; CVB, LSV, PVM, PMV and ASPV (subgroup IIa) and LVX (subgroup IIb). The third cluster carries the most diverse of TGBV comprising furoviruses PCV, PMTV and BSBV (subgroup IIIa) and hordeiviruses PSLV, BSMV and LRSV (subgroup IIIb). The phylogenetic relationships of triple gene block viruses (TGBV) based on the TGB 1 homolog gene indicates a convergent evolution.

Amino Acid Sequence↗
PubMedDate not supplied

[A few viral infections in the recent epidemiological evolution (author's transl)].

In the study we presented a few infections of viral etiology that showed evident epidemiological evolutions during the last ten years. We refered of a disease nearly eradicated, of one that can be eradicated, and of a group of infections that at present cannot be eradicated. The first is poliomyelitis, the second is measles, the third is represented by viral infections connected with the respiratory tract. As for the first disease, the sistematic immunoprophilaxis applyed in different countries of the world on one hand stopped the transmission of wild polioviruses and on the other created an immunological barrier in those countries where polio vaccination is maintained, as demonstrated by statistics revealing the absence or low incidence of this disease. As for the epidemiological evolution of measles, after considering the incidence due to age, environment, social-hygienic conditions, mortality etc..., we refered in particular of a vaccination that took place in USA where the disease decreased with 1968 then rised next year a pause of the vaccination program. A second cycle of vaccinations against measles revealed in 1972 a decrease of the disease this signifying the importance of the vaccination in stopping, reducing or modifying the epidemiology of measles. The epidemiological conditions of respiratory infections are completely different due to the variety of the etiological factors, the difficulty in preparing aspecific vaccines, and the impossibility in recognising clinical forms caused by these viruses. All these factors, impede, actually, a complete eradication.

Africa↗
PubMed1998

Evolution of hypervariable region 1 of hepatitis C virus in primary infection.

The hypervariable region 1 (HVR-1) of the putative envelope encoding E2 region of hepatitis C virus (HCV) RNA was analyzed in sequential samples from three patients with acute type C hepatitis infected from different sources to address (i) the dynamics of intrahost HCV variability during the primary infection and (ii) the role of host selective pressure in driving viral genetic evolution. HVR-1 sequences from 20 clones per each point in time were analyzed after amplification, cloning, and purification of plasmid DNA from single colonies of transformed cells. The intrasample evolutionary analysis (nonsynonymous mutations per nonsynonymous site [Ka], synonymous mutations per synonymous site [Ks], Ka/Ks ratio, and genetic distances [gd]) documented low gd in early samples (ranging from 2. 11 to 7.79%) and a further decrease after seroconversion (from 0 to 4.80%), suggesting that primary HCV infection is an oligoclonal event, and found different levels and dynamics of host pressure in the three cases. The intersample analysis (pairwise comparisons of intrapatient sequences; rKa, rKs, rKa/rKs ratio, and gd) confirmed the individual features of HCV genetic evolution in the three subjects and pointed to the relative contribution of either neutral evolution or selective forces in driving viral variability, documenting that adaptation of HCV for persistence in vivo follows different routes, probably representing the molecular counterpart of the viral fitness for individual environments.

Adolescent↗
PubMed1996

Integration of multiple repeats of geminiviral DNA into the nuclear genome of tobacco during evolution.

Integration of viral DNA into the host nuclear genome, although not unusual in bacterial and animal systems, has surprisingly not been reported for plants. We have discovered geminvirus-related DNA (GRD) sequences, in the form of distinct sets of multiple direct repeats comprising three related repeat classes, situated in a unique locus in the Nicotiana tabacum (tobacco) nuclear genome. The organization of these sequences is similar or identical in eight different tobacco cultivars we have examined. DNA sequence analysis reveals that each repeat has sequences most resembling those of the New World geminiviral DNA replication origin plus the adjacent AL1 gene, encoding the viral replication protein. We believe these GRD sequences originated quite recently in Nicotiana evolution through integration of geminiviral DNA by some combination of the processes of illegitimate recombination, amplification, deletions, and rearrangements. These events must have occurred in plant tissue that was subsequently able to contribute to meristematic tissue yielding gametes. GRD may have been retained in tobacco by selection or by random fixation in a small evolving population. Although we cannot detect transcription of these sequences, this does not exclude the possibility that they may originally have been expressed.

Amino Acid Sequence↗
PubMed2003

[The mechanism of antigenic shift and drift of human influenza virus].

Influenza virus has a remarkable ability in escaping host defense mechanisms by altering its the antigenic character. The molecular mechanisms by which viruses alter their antigenic character form an important subject of study since they ultimately control epidemics of influenza. 1) We showed how the 1993/1994 antigenic variant viruses appeared from the 1991 virus by analyzing human sera with a chimeric protein method. 2) We introduced random one-point amino acid changes on the A/Aichi/2/68(A/Aichi/68) HA protein by PCR mutation methods and estimated the viability of the H3HA protein resulting from theses amino acid changes and to determine which changes are allowed during evolution of the H3HA protein.

Amino Acid Sequence↗
PubMed2006

Structure, function and evolution of the hemagglutinin-esterase proteins of corona- and toroviruses.

Virus attachment to host cells is mediated by dedicated virion proteins, which specifically recognize one or, at most, a limited number of cell surface molecules. Receptor binding often involves protein-protein interactions, but carbohydrates may serve as receptor determinants as well. In fact, many different viruses use members of the sialic acid family either as their main receptor or as an initial attachment factor. Sialic acids (Sias) are 9-carbon negatively-charged monosaccharides commonly occurring as terminal residues of glycoconjugates. They come in a large variety and are differentially expressed in cells and tissues. By targeting specific Sia subtypes, viruses achieve host cell selectivity, but only to a certain extent. The Sia of choice might still be abundantly present on non-cell associated molecules, on non-target cells (including cells already infected) and even on virus particles themselves. This poses a hazard, as high-affinity virion binding to any of such "false'' receptors would result in loss of infectivity. Some enveloped RNA viruses deal with this problem by encoding virion-associated receptor-destroying enzymes (RDEs). These enzymes make the attachment to Sia reversible, thus providing the virus with an escape ticket. RDEs occur in two types: neuraminidases and sialate-O-acetylesterases. The latter, originally discovered in influenza C virus, are also found in certain nidoviruses, namely in group 2 coronaviruses and in toroviruses, as well as in infectious salmon anemia virus, an orthomyxovirus of teleosts. Here, the structure, function and evolution of viral sialate-O-acetylesterases is reviewed with main focus on the hemagglutinin-esterases of nidoviruses.

Amino Acid Sequence↗
PubMed2006

Co-evolution of nelfinavir-resistant HIV-1 protease and the p1-p6 substrate.

The selective pressure of the competitive protease inhibitors causes both HIV-1 protease and occasionally its substrates to evolve drug resistance. We hypothesize that this occurs particularly in substrates that protrude beyond the substrate envelope and contact residues that mutate in response to a particular protease inhibitor. To validate this hypothesis, we analyzed substrate and protease sequences for covariation. Using the chi2 test, we show a positive correlation between the nelfinavir-resistant D30N/N88D protease mutations and mutations at the p1-p6 cleavage site as compared to the other cleavage sites. Both nelfinavir and the substrate p1-p6 protrude beyond the substrate envelope and contact residue 30, thus possibly making the p1-p6 cleavage site more vulnerable to co-evolution.

Drug Resistance, Viral↗