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 91 records · Page 5Linked to original sources
PubMed1997

Rapid evolution of viral RNA genomes.

Mutation rates during RNA virus replication are several orders of magnitude larger than those operating during replication of cellular DNA. This results in the continuous generation of mutant genomes and in their rating in competition with other variants present and arising in the population. The dynamic mutant distributions that constitute RNA virus populations are termed quasispecies. This concept has facilitated links between population genetics and virology and has a number of important implications for viral pathogenesis and the control of viral disease. One of them is that the mutant spectra in RNA viruses constitute large reservoirs of genetic and phenotypic variants with potentially altered biological properties. Individual mutants kept in a low proportion under a set of environmental conditions may become dominant following an environmental change. Relevant to this review are possible links between the alteration of quasispecies distributions and nutritional deficiencies and oxidative stress in cells. In addition to being a possible mechanism of viral pathogenesis, oxidative stress, and other environmental modifications resulting from nutritional imbalances, may promote population disequilibrium in replicating viruses. In particular, the increased mutagenesis mediated by oxidative DNA damage could also affect replicating RNA and integrated provirus, extending the mutant repertoire of viruses. Also, the impairment of humoral and cellular immune functions may delay or prevent viral clearance, leading to an expanded representation of viral mutants in the infected organism. Thus, nutritional deficiencies are a potential source of viral mutants with altered biological properties.

Biological Evolution↗
PubMed2026

Effect of inhaled interferon-β1a on SARS-CoV-2 diversity and evolution.

Interferon resistance has been implicated in SARS-CoV-2 escape from innate immunity, but exogenous interferon's impact on viral evolution and diversity is unknown. SNG001, an inhaled interferon-β1a treatment, was evaluated in the ACTIV-2/A5401 randomized controlled trial of therapeutics for COVID-19. We measured viral kinetics and performed whole-genome sequencing on longitudinal nasal swabs collected from ACTIV-2 participants who received either SNG001 or placebo to assess viral sequence diversity. No difference in nasal viral load decay was detected between study arms when stratifying by SARS-CoV-2 variant or by viral culture conversion. Compared to placebo participants, the SNG001-treated participants displayed significantly lower nonsynonymous amino acid average pairwise distance, indicating lower sequence diversity. Similarly, SNG001-treated individuals also developed numerically fewer nonsynonymous mutations during their infection in ORF1a, ORF1b, Spike, and Nucleocapsid. No specific emerging SARS-CoV-2 nonsynonymous amino acid changes indicating signatures of viral escape were enriched in those receiving SNG001. These in vivo data provide an intriguing signal that exogenous interferon-β1a may restrict SARS-CoV-2 viral diversity and add to growing evidence that interferon levels play a critical role in antiviral responses during COVID-19.IMPORTANCESARS-CoV-2 encodes several genes which can antagonize the interferon signaling cascade, preventing it from activating antiviral responses and thereby facilitating viral establishment and dissemination. It is unknown how the administration of exogenous interferon might affect viral evolution and immune escape. ACTIV-2/A5401 represents a unique opportunity to study the virologic effects of interferon treatment in a rigorous randomized, placebo-controlled clinical trial setting. Our characterization of longitudinal nasal samples shows that interferon-treated individuals had lower viral diversity and no evidence of viral escape mutations.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04518410.

Humans↗
PubMed2002

Evolution of viral quasispecies in four dominant HlA-A2 restricted T cell epitopes is not a major reason for viral persistence in interferon-treated patients with chronic hepatitis C.

In most patients, chronic hepatitis C virus (HCV) infection persists despite antiviral treatment with interferon-alpha (IFN-alpha) and ribavirin. The aim of the study was to determine whether HCV could evade cellular immune responses through mutations within T cell epitopes. Viral sequences flanking four major CTL epitopes within the HCV core and envelope regions were analyzed by PCR amplification, cloning and sequencing in seven HLA-A2 positive HCV patients before, during and after antiviral therapy. In addition, cytotoxic T lymphocyte precursor (CTLp) frequencies specific to these epitopes were quantitated by ELISPOT. A total of 13 coding mutations were observed among 650 cloned and sequenced PCR products under or post IFN treatment but no clear selection of viral variants. In detail, the diversity of quasispecies in the two core epitopes remained fairly stable over time despite variable CTLp induction in some individuals. The overall mutation rate in the two envelope epitopes was higher but there was no correlation with specific CTLp frequencies. In conclusion, although evolution of the viral quasispecies during and after antiviral therapy was demonstrated, immune evasion by epitope specific mutations seemed to be not common in interferon nonresponders because the viral complexity did not increase.

Adult↗
PubMed1999

Different trajectories of parallel evolution during viral adaptation.

The molecular basis of adaptation is a major focus of evolutionary biology, yet the dynamic process of adaptation has been explored only piecemeal. Experimental evolution of two bacteriophage lines under strong selection led to over a dozen nucleotide changes genomewide in each replicate. At least 96 percent of the amino acid substitutions appeared to be adaptive, and half the changes in one line also occurred in the other. However, the order of these changes differed between replicates, and parallel substitutions did not reflect the changes with the largest beneficial effects or indicate a common trajectory of adaptation.

Adaptation, Physiological↗
PubMed2002

Imbroglios of viral taxonomy: genetic exchange and failings of phenetic approaches.

The practice of classifying organisms into hierarchical groups originated with Aristotle and was codified into nearly immutable biological law by Linnaeus. The heart of taxonomy is the biological species, which forms the foundation for higher levels of classification. Whereas species have long been established among sexual eukaryotes, achieving a meaningful species concept for prokaryotes has been an onerous task and has proven exceedingly difficult for describing viruses and bacteriophages. Moreover, the assembly of viral "species" into higher-order taxonomic groupings has been even more tenuous, since these groupings were based initially on limited numbers of morphological features and more recently on overall genomic similarities. The wealth of nucleotide sequence information that catalyzed a revolution in the taxonomy of free-living organisms necessitates a reevaluation of the concept of viral species, genera, families, and higher levels of classification. Just as microbiologists discarded dubious morphological traits in favor of more accurate molecular yardsticks of evolutionary change, virologists can gain new insight into viral evolution through the rigorous analyses afforded by the molecular phylogenetics of viral genes. For bacteriophages, such dissections of genomic sequences reveal fundamental flaws in the Linnaean paradigm that necessitate a new view of viral evolution, classification, and taxonomy.

Bacteriophages↗
PubMed2002

Origin and evolution of viral interleukin-10 and other DNA virus genes with vertebrate homologues.

Phylogenies of gene families including members in both vertebrates and DNA viruses of the poxvirus and/or herpesvirus families showed that the viral genes originated at widely different times over the history of life. Certain of these viral genes (for example, the genes encoding the large and small subunits of ribonucleoside-diphosphate reductase) originated before animals diverged from fungi, while others originated much more recently. The most striking examples of recent origin involved viral genes encoding the cytokine interleukin-10 (IL-10), which originated independently in viruses at least three times since the divergence of the orders of eutherian mammals, presumably by viral capture of host genes. In certain domains, viral IL-10 genes showed significantly higher rates of nonsynonymous substitution than their nearest mammalian homologues. Though the mutation rate in these viral genes is up to 20 times that of the corresponding mammalian genes, a high mutation rate alone did not account for these differences because they were not seen in all domains. Rather, in certain domains it appears that functional constraints present in the case of mammalian IL-10 are relaxed in the case of the viral homologues. Furthermore, a nonrandom pattern of change with respect to amino acid residue charge in the N-terminal portion of the mature protein has occurred repeatedly in independently derived viral IL-10 genes, strongly suggesting that positive selection has led to divergence of this functionally important domain in viral IL-10.

Antigens, CD↗
PubMed2025

Characterisation of a persistent SARS-CoV-2 infection lasting more than 750 days in a person living with HIV: a genomic analysis.

BACKGROUND: People who are immunocompromised can develop persistent SARS-CoV-2 infections. Several viral mutations accumulated during the course of such persistent infections have also been observed in prominent variants of concern (VOCs). Here, we characterise persistent infection and viral evolution of SARS-CoV-2 lasting more than 750 days in a person with advanced HIV-1 infection. METHODS: Between March, 2021, and July, 2022, eight clinical specimens were collected from a person living with HIV, neither receiving antiretroviral therapy nor virally suppressed, and presumed to have been initially infected with SARS-CoV-2 in mid-May, 2020. Viral RNA was extracted from each swab and an amplicon-based sequencing approach was used for genomic analysis of SARS-CoV-2. Variable sites were characterised at the consensus and subconsensus levels, and phylogenetic tools were applied to analyse viral evolution. Publicly available SARS-CoV-2 sequences from GenBank were leveraged to contextualise our sequenced samples and identify any potential evidence of transmission. FINDINGS: Genomes formed a monophyletic cluster in the B.1 lineage. 68 consensus and 67 subconsensus single nucleotide variants were observed over the course of infection. The intrahost clock rate remained similar to that of the interhost rate in contemporaneous community sequences (6·74 × 10-4 [95% credible interval 5·05 × 10-4 to 8·54 × 10-4] substitutions per site per year vs 6·11 × 10-4 [5·54 × 10-5 to 6·66 × 10-4]). Mutations grouped into two distinct subpopulations present throughout infection. 10 non-synonymous mutations in the spike protein gene were at positions in common with those defining the omicron lineage (BA.1 or BA.2), of which nine were present before November, 2021. Nine of 18 substitutions present throughout infection were rare in online databases, suggesting a lack of long transmission chains descending from this individual. INTERPRETATION: Convergent SARS-CoV-2 evolution, both in and outside the spike protein, observed in this study suggests parallels with the evolutionary process leading to emergence of the omicron VOC. The inferred absence of onward infections might indicate a loss of transmissibility during adaptation to a single host. Our results underscore the importance of appropriate treatment to cure persistent SARS-CoV-2 infections and monitoring them to understand how mutations contribute to viral adaptation. FUNDING: National Institute of General Medical Sciences of the National Institutes of Health, Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, MassCPR, and Morris Singer Foundation.

Humans↗
PubMed2004

CD8 epitope escape and reversion in acute HCV infection.

In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.

Acute Disease↗
PubMed2026

SARS-CoV-2 intra-host variation shows evidence of transmission and convergent evolution in a university surveillance cohort.

Monitoring and understanding the transmission and evolution of SARS-CoV-2 remains a significant public health priority. Within-host genetic variation provides insight into viral evolution during infection and may help infer transmission events. In this study, we analysed intra-host variation in SARS-CoV-2 genome sequences from Boston University's testing mandate. Focusing on intra-host single nucleotide variants (iSNVs), we inferred transmission events and assessed the selective forces shaping within-host viral evolution. To minimize false-positive iSNVs resulting from systematic biases, we implemented stringent data filtering and developed a heuristic to exclude contamination-derived artefacts arising from batched sequencing. We find that intra-host variation is limited and infrequently transmitted during acute infections, suggesting that shared iSNVs serve as highly specific but insensitive markers of transmission. We also observed incomplete purifying selection shaping within-host diversity, with the loci most affected changing among variants of concern. Finally, we identified a highly recurrent iSNV (G11083T) which may represent a site of positive selection. Our results highlight that within-host variation provides insight into within-host pathogen evolution, in spite of its limited use in genomic epidemiology.

SARS-CoV-2↗
PubMed2005

Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection.

Studies in acute human immunodeficiency virus type 1 (HIV-1) infection indicate viral evolution under CD8 T-cell immune selection pressure, but the effects of ongoing immune pressure on epitope evolution during chronic infection are not well described. In this study, we performed a detailed longitudinal analysis of viral sequence variation within persistently targeted cytotoxic T-lymphocyte (CTL) epitopes in two HIV-1-infected persons during 6 years of persistent viremia. Responses were quantitated using freshly isolated peripheral blood lymphocytes in direct lytic assays as well as by gamma interferon (IFN-gamma) Elispot assays on cryopreserved cells. Seven targeted epitopes were identified in each person. In the majority of cases, the dominant epitope sequence did not change over time, even in the presence of responses of sufficient magnitude that they were detectable using fresh peripheral blood mononuclear cells in direct lytic assays. Only 4 of the 14 autologous epitopes tested represented potential CTL escape variants; however, in most cases strong responses to these epitopes persisted for the 6 years of study. Although persistent IFN-gamma responses were detected to all epitopes, direct lytic assays demonstrated declining responses to some epitopes despite the persistence of the targeted sequence in vivo. These data indicate limited viral evolution within persistently targeted CD8 T-cell epitopes during the chronic phase of infection and suggest that these regions of the virus are either refractory to sequence change or that persistently activated CD8 T-cell responses in chronic infection exert little functional selection pressure.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Evolution of viral hepatitis B markers in children infected with HBV in the first two years of life].

Circumstances of acquiring an infection, spontaneous evolution of markers during 6 years of follow-up, laboratory findings and results of liver biopsies were analysed in 51 children infected with HBV during the first two years of life; 76.5% of them developed chronic carrier state. ALAT values were periodically increased in 34 children (66.6%) and elimination of HBeAg i HBsAg occurred in 17 (33.3%) and 12 children (23.5%), respectively, during the first year of follow-up. Seroconversion was observed only in a few cases in the subsequent years. Anti-HBc IgM antibodies were detectable for a mean period of less than 7 months (p < 0.02) after diagnosis of infection.

Chronic Disease↗
PubMed1995

Evolution of viral DNA-dependent RNA polymerases.

The DNA-dependent RNA polymerase (DdRP or RNAP) is an essential enzyme of transcription of replicating systems of prokaryotic and eukaryotic organisms as well as cytoplasmic DNA viruses. DdRPs are complex multisubunit enzymes consisting of 8-14 subunits, including two large subunits and several smaller polypeptides (small subunits). An extensive search between the amino acid sequences of the known largest subunit of DNA-dependent RNA polymerases (RPO1) of different organisms indicates that all these polypeptides possess a universal heptapeptide NADFDGD in domain D. All RPO1 harbor a second well-conserved hexapeptide RQP(TS)LH upstream (26-31 amino acids) of the universal motif. The genes encoding the largest subunit of DdRP of insect iridescent virus type 6 (IIV6), fish lymphocystis disease virus (LCDV), and molluscum contagiosum virus (MCV-1), all members of the group of cytoplasmic DNA viruses, were identified by PCR technology. With the exception of IIV6, all other viral RPO1 possess the two C-terminal conserved regions G and H. The lack of C-terminal repetitive heptapeptide (YSPTSPS), which is a common feature of the largest subunit of eukaryotic RNAPII, is an additional characteristic of RPO1 proteins of LCDV and of MCV-1. All viral RPO1 proteins were found to be lacking the amino acid N at a distinct position in domain F. This amino acid is known to be highly conserved in alpha-amanitin-sensitive eukaryotic RNA polymerases II. Comparison of the amino acid sequences of the RPO1 polypeptides of IIV6, LCDV, and MCV-1 with the corresponding prokaryotic, eukaryotic, and viral proteins revealed differences in amino acid similarity and phylogenetic relationships. IIV6 RPO1 possesses the closest similarity to the homologous subunit of eukaryotic RNAPII and lower but also significant similarity to that of eukaryotic RNAPI and RNAPIII, archaeal, eubacterial, and viral polymerases. The similarity between RPO1 of IIV6 and the cellular polymerase subunits is consistently higher than to the RPO1 of other cytoplasmic DNA viruses, for example, vaccinia and variola virus, African swine fever virus (ASFV), and MCV-1. The RPO1 of LCDV shows the highest similarity to the RPO1 of IIV6 and significant lower similarity to the eukaryotic polymerases II and III as well as to the archaebacteral subunit. However, it is still considerably more similar to the cellular polymerase subunits than to the homologous viral proteins. The RPO1 of IIV6 possesses more similarity to cellular polymerases than the complete RPO1 of LCDV, indicating that there is a substantial difference in the organization of the RPO1 genes between these members of two genera of the Iridoviridae family. Analysis of the MCV-1 RPO1 revealed high amino acid homologies to the corresponding polypeptides of vaccinia and variola virus. The viral RPO1 proteins, including vaccinia and variola virus, MCV-1, ASFV, IIV6, and LCDV, share the common feature of showing the highest similarity to the largest subunit of eukaryotic RNAPII than to that of RNAPI, RNAPIII, and RPO1 of archaebacterias, eubacterias, ASFV, IIV6, and LCDV. Evolution of the individual largest subunit of DdRPs was tentatively investigated by generating phylogenetic trees using multiple amino acid alignments. These indicate that the RPO1 proteins of IIV6 and LCDV might have evolved from the largest subunit of eukaryotic RNAPII after divergence from the homologous subunits of RNAPI and RNAPIII. In contrast, evolutionary development of the RPO1 of vaccinia and variola virus, MCV-1, and ASFV seems to be quite different, with their common ancestor diverging from cellular homologues before the separation of the three types of eukaryotic ploymerases and having probably diverged earlier from their common lineage with cellular proteins.

Amino Acid Sequence↗
PubMedDate not supplied

Aspect of the evolution of viral hepatitis two years after the acute phase.

A group of 214 nonselected former patients with viral hepatitis of which 15 HBsAg negative and 62 HBsAg positive, was studied prospectively by following the evolutive variations between the first and second year after the acute phase of disease. In both groups the percentage of cured cases increased moderately but the evolutive process toward the chronic stage was observed to reappear in some of the cases apparently cured thus proving that the process of becoming chronic is not completed within 1 year after the acute phase. The percentage of chronic cases after HBsAg positive hepatitis is clearly higher than after HBsAg negative hepatitis the difference being more evident in active chronic hepatitis. The risk of becoming chronic is greater after HBsAg positive viral hepatitis with prolonged clinical forms and the HB antigen also persists longer in the serum. In conclusion the necessity of clinical and biologic control of all former patients with viral hepatitis for at least 2 years after the acute phase is strongly emphasized.

Adult↗
PubMed1996

Relation between changes in cellular load, evolution of viral phenotype, and the clonal composition of virus populations in the course of human immunodeficiency virus type 1 infection.

The relationship between the evolution of human immunodeficiency virus type 1 (HIV-1) biologic phenotype, changes in the proportion of infected peripheral blood mononuclear cells, and the relative contribution of non-syncytium-inducing (NSI) and syncytium-inducing (SI) HIV-1 variants to virus load was studied during the course of HIV-1 infection. In 65 HIV-1-infected subjects, the proportion of infected CD4 T cells was higher in persons who carried SI variants. Longitudinal studies revealed that the emergence of SI HIV-1 variants can occur at relatively low numbers of HIV-1-infected cells. Emergence of SI variants frequently coincided with an increase of virus load due to an expansion of both NSI and SI variants, although the contribution of SI viruses to the total virus population significantly increased with time after SI phenotype conversion. These data indicate that NSI to SI phenotype conversion, rather than resulting from high virus load, is part of the sequence of events that leads to increased virus load and CD4 cell depletion.

CD4 Lymphocyte Count↗