Virus, the primordial parasite, and man.
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Adenoviruses, Canine↗
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Results for “virus evolution”
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Evolution of two amino acid positions governing broad neutralization resistance in a strain of feline immunodeficiency virus over 7 years of persistence in cats.
Fresh isolates of lentiviruses are characterized by an outstanding resistance to antibody-mediated neutralization. By investigating the changes that occurred in a neutralization-sensitive tissue culture-adapted strain of feline immunodeficiency virus after it was reinoculated into cats, a previous study had identified two amino acid positions of the surface glycoprotein (residues 481 and 557) which govern broad neutralization resistance (BNR) in this virus. By extending the follow-up of six independently evolving in vivo variants of such virus for up to 92 months, we now show that the changes at the two BNR-governing positions not only were remarkably stereotyped but also became fixed in an ordered sequential fashion with the duration of in vivo infection. In one variant, the two positions were also seen to slowly alternate at determining BNR. Evidence that evolution at the BNR-governing positions was accompanied, and possibly driven, by changes in the antigenic makeup of the viral surface brought about by the mutations at such positions is also presented.
Amino Acid Substitution↗
Restoration of native folding of single-stranded DNA sequences through reverse mutations: an indication of a new epigenetic mechanism.
We used in vivo (biological), in silico (computational structure prediction), and in vitro (model sequence folding) analyses of single-stranded DNA sequences to show that nucleic acid folding conservation is the selective principle behind a high-frequency single-nucleotide reversion observed in a three-nucleotide mutated motif of the Maize streak virus replication associated protein (Rep) gene. In silico and in vitro studies showed that the three-nucleotide mutation adversely affected Rep nucleic acid folding, and that the single-nucleotide reversion [C(601)A] restored wild-type-like folding. In vivo support came from infecting maize with mutant viruses: those with Rep genes containing nucleotide changes predicted to restore a wild-type-like fold [A(601)/G(601)] preferentially accumulated over those predicted to fold differently [C(601)/T(601)], which frequently reverted to A(601) and displaced the original population. We propose that the selection of native nucleic acid folding is an epigenetic effect, which might have broad implications in the evolution of plants and their viruses.
DNA, Viral↗
Mathematical approaches in the study of viral kinetics and drug resistance in HIV-1 infection.
We review some crucial aspects of drug therapy and viral resistance that have been investigated within the framework developed for the modelling of virus kinetics. First, we give a general overview on the use of mathematical models in the field of HIV research. We seek to identify the factors that determine the steady state virus load and show that stable reductions during antiviral therapy are difficult to explain within the standard model of virus dynamics. We discuss possible extensions that enable the models to account for the moderately reduced virus loads during non-suppressive treatment and argue that the residual viremia under suppressive treatment can probably be attributed to the survival of long-lived infected cells, rather than to new rounds of replication. Next, we address the emergence of resistance during suppressive therapy and demonstrate that the resistant virus is more likely to be present already at the start of treatment than to be generated during therapy. The appearance of resistance after a prolonged period of initial suppression indicates that drug efficacy is not continuously maintained over time. We investigate the potential risks and benefits of therapy interruptions. Considering the effect of recombination, we argue that it probably decelerates, rather than accelerates the evolution of multidrug-resistant virus. We also review state-of-the-art methods for the estimation of fitness, which is crucial to the understanding of the emergence of resistance during therapy or the re-emergence of wild type upon the cessation of therapy.
Anti-HIV Agents↗
Antiviral antibody responses: the two extremes of a wide spectrum.
Viruses elicit a diverse spectrum of antiviral antibody responses. In this review, we discuss two widely used experimental model systems for viral infections - non-cytopathic lymphocytic choriomeningitis virus (LCMV) and acutely cytopathic vesicular stomatitis virus (VSV) - to analyse two fundamentally different types of antiviral antibody response. The basic principles found in these model infections are discussed in the context of other viral infections, and with regard to protective neutralizing versus non-protective enzyme-linked immunosorbent assay (ELISA)-detected antibody responses. Issues of antibody specificity, affinity and avidity, maturation and escape are discussed in the context of co-evolution of the host and viruses.
Animals↗
[Presence of HBsAg in lymphocyte cultured from patients infected with human immunodeficiency virus (HIV)].
The behavior of the hepatitis B virus was investigated in mononuclear cell cultures in nine patients infected by the human immunodeficiency virus. Although only one of them was a carrier of HBsAg and four had anti-HBs in their sera, HBsAg was detected in the supernatant of the cultures from all patients. These results suggest that mononuclear cells might act as a reservoir for hepatitis B virus, and that the concomitant infection by this virus and human immunodeficiency virus may alter the natural evolution of any of both conditions.
Adult↗
Isolation and characterization of Dobrava hantavirus carried by the striped field mouse (Apodemus agrarius) in Estonia.
Dobrava hantavirus (DOB) was isolated from the striped field mouse (Apodemus agrarius) trapped on Saaremaa Island, Estonia, and its genetic and antigenic characteristics were subsequently analysed. Phylogenetic analysis showed that the Estonian DOB strain, together with several wild strains carried by Apodemus agrarius, forms a well-supported lineage within the DOB clade. The topography of the trees calculated for the S, M and L nucleotide sequences of the Estonian DOB suggests a similar evolutionary history for all three genes of this virus and, therefore, the absence of heterologous reassortment in its evolution. A cross-neutralization comparison of the Estonian virus with the prototype DOB, isolated from a yellow-necked mouse (A. flavicollis) in Slovenia, revealed 2- to 4-fold differences in the end-point titres of rabbit and human antisera. When studied with a panel of 25 monoclonal antibodies (MAbs), the Estonian and Slovenian DOB isolates showed similar antigenic patterns that could be distinguished by two MAbs. Genetic comparison showed sequence differences in all three genome segments of the two DOB isolates, including an additional N-glycosylation site in the deduced sequence of the G2 protein from the Estonian virus. Whether any of these mutations relates to the different rodent hosts rather than to the distant geographical origin of the two isolates remains to be resolved. Taken together, our observations suggest that A. agrarius, which is known to harbour Hantaan virus in Asia, carries another hantavirus, DOB, in north-east Europe.
Animals↗
Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection.
Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population studies showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data and functional studies of CD8 T-cell responses to demonstrate that allele-specific immune pressures also select for mutations flanking CD8 epitopes that impair antigen processing. In persons expressing HLA-A3, we demonstrate consistent selection for a mutation in a C-terminal flanking residue of the normally immunodominant Gag KK9 epitope that prevents its processing and presentation, resulting in a rapid decline in the CD8 T-cell response. This single amino acid substitution also lies within a second HLA-A3-restricted epitope, with the mutation directly impairing recognition by CD8 T cells. Transmission of the mutation to subjects expressing HLA-A3 was shown to prevent the induction of normally immunodominant acute-phase responses to both epitopes. However, subsequent in vivo reversion of the mutation was coincident with delayed induction of new CD8 T-cell responses to both epitopes. These data demonstrate that mutations within the flanking region of an HIV-1 epitope can impair recognition by an established CD8 T-cell response and that transmission of these mutations alters the acute-phase CD8(+) T-cell response. Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes.
Amino Acid Sequence↗
Vesicular stomatitis New Jersey virus glycoprotein gene sequence and neutralizing epitope stability in an enzootic focus.
Vesicular stomatitis New Jersey (VS NJ) virus is capable of undergoing rapid evolution in nature and therefore has the potential for antigenic variation. We selected an area of Costa Rica where VS NJ virus is enzootic to study whether this virus used the mechanism of antigenic variation to persist in nature. Three sentinel herds and three nonsentinel herds were observed from 1986 to 1988. Eleven VS NJ virus isolates were collected from naturally infected cattle. Remarkably, nine animals that were bled prior to reinfection with VS NJ virus had neutralizing antibody titers up to 1: 102,400 yet virus was isolated from, and disease was observed in, these animals. Sequence analysis of the portion of the glycoprotein gene coding for the neutralizing epitopes demonstrated that all virus isolates were 98-100% similar with no indication of specific genetic variation. The 3' end of the glycoprotein gene also remained stable in that all isolates were again 98-100% similar in nucleotide sequence. Each isolate was neutralized to equivalent titers with monoclonal antibodies directed against four neutralizing epitopes on the glycoprotein. Additionally, preisolation sera from each animal were able to neutralize the virus that caused the subsequent disease. These results provide evidence that antigenic variation is not a mechanism used by VS NJ virus to persist in an enzootic focus of Costa Rica.
Animals↗
The fastest genome evolution ever described: HIV variation in situ.
Human immunodeficiency virus is an RNA virus in which the degree of genetic variation observed is phenomenal--up to 20% within an infected individual. This is essentially due to remorseless cycles of viral replication, most probably due to chronic activation of the immune system. It can be estimated that the number of variants in existence worldwide must be in excess of 10(14)-10(18), and given the nature of RNA viruses even more novel variants should emerge.
Biological Evolution↗
The palm subdomain-based active site is internally permuted in viral RNA-dependent RNA polymerases of an ancient lineage.
Template-dependent polynucleotide synthesis is catalyzed by enzymes whose core component includes a ubiquitous alphabeta palm subdomain comprising A, B and C sequence motifs crucial for catalysis. Due to its unique, universal conservation in all RNA viruses, the palm subdomain of RNA-dependent RNA polymerases (RdRps) is widely used for evolutionary and taxonomic inferences. We report here the results of elaborated computer-assisted analysis of newly sequenced replicases from Thosea asigna virus (TaV) and the closely related Euprosterna elaeasa virus (EeV), insect-specific ssRNA+ viruses, which revise a capsid-based classification of these viruses with tetraviruses, an Alphavirus-like family. The replicases of TaV and EeV do not have characteristic methyltransferase and helicase domains, and include a putative RdRp with a unique C-A-B motif arrangement in the palm subdomain that is also found in two dsRNA birnaviruses. This circular motif rearrangement is a result of migration of approximately 22 amino acid (aa) residues encompassing motif C between two internal positions, separated by approximately 110 aa, in a conserved region of approximately 550 aa. Protein modeling shows that the canonical palm subdomain architecture of poliovirus (ssRNA+) RdRp could accommodate the identified sequence permutation through changes in backbone connectivity of the major structural elements in three loop regions underlying the active site. This permutation transforms the ferredoxin-like beta1alphaAbeta2beta3alphaBbeta4 fold of the palm subdomain into the beta2beta3beta1alphaAalphaBbeta4 structure and brings beta-strands carrying two principal catalytic Asp residues into sequential proximity such that unique structural properties and, ultimately, unique functionality of the permuted RdRps may result. The permuted enzymes show unprecedented interclass sequence conservation between RdRps of true ssRNA+ and dsRNA viruses and form a minor, deeply separated cluster in the RdRp tree, implying that other, as yet unidentified, viruses may employ this type of RdRp. The structural diversification of the palm subdomain might be a major event in the evolution of template-dependent polynucleotide polymerases in the RNA-protein world.
Amino Acid Motifs↗
HTLV-II seroprevalence in pygmies across Africa since 1970.
HTLV-II-specific antibodies, with patterns similar to those in the Americas, were present in sera collected about 1970 from Bambuti pygmies in Zaire (14/102; 14%) and from pygmies in Cameroon (5/214; 2.3%), and were more prevalent than HTLV-I. In the Central African Republic, 504 pygmies were HTLV negative. After finding of 4 HTLV-II seropositives among 12 Bambuti pygmies sampled in 1991, this established that HTLV-II or a related retrovirus is present as an ancient endemic in some, but not all, insulated groups of African pygmies, similar to the HTLV-II distribution in Amerindian populations. The endemic among the oldest inhabitants of central Africa, and the occasional and scattered occurrence of apparent HTLV-II among predominant HTLV-I in other Africans, fit well with an ancient African virus and not with importation from the New World. Theories on the origin and evolution of the primate T-lymphotropic viruses (PTLVs) should take into account the longstanding presence of HTLV-II-type viruses in both the Old and New World. Present serology suggests identity of the African viruses with HTLV-II, but their assignment to a new HTLV type is open should genetic analysis show strong divergence from American HTLV-II. Clinical expression, if any, remains to be studied.
Blotting, Western↗
R5 to X4 switch of the predominant HIV-1 population in cellular reservoirs during effective highly active antiretroviral therapy.
HIV-1 coreceptor usage plays a critical role for virus tropism and pathogenesis. A switch from CCR5 to CXCR4-using viruses can occur in the natural course of infection and correlates with subsequent disease progression. To investigate whether HIV-1 genetic evolution might lead to changes in virus coreceptor usage during highly active antiretroviral therapy (HAART), a longitudinal genotypic analysis of the virus found in cellular reservoirs was conducted in 32 patients with undetectable viral loads on HAART for 5 years. The genotype of the 3rd variable region of the env gene predicting coreceptor usage was retrospectively determined in the plasma or in peripheral blood mononuclear cells (PBMC) at baseline and then in PBMCs at months 30 and 60 of HAART. There was a switch from R5 to X4 variants in 11 of the 23 patients who harbored a majority virus population of R5 variants at baseline. X4 variants remained predominant in the 9 patients who harbored mainly X4 variants at baseline. The patients harboring predominantly X4 variants during HAART, either from baseline or after an R5 to X4 switch, tended to have lower CD4+ T-cell counts on HAART than did patients harboring continuously a majority population of R5 variants. These results suggest that potent antiretroviral therapy produces the conditions necessary for the gradual emergence of X4 variants in cellular reservoirs.
Acquired Immunodeficiency Syndrome↗
Aujeszky's disease vaccination and differentiation of vaccinated from infected pigs.
In this paper, the use of a glycoprotein E (gE)-deleted vaccine to eradicate Aujeszky's disease virus (ADV) or pseudorabies virus in swine is described. In regions where there is a dense population of swine, ADV is highly prevalent and intensive vaccination with such a marker vaccine has resulted, in several countries, in a decrease of the field virus prevalence to a sufficiently low level so that culling becomes economically feasible. The evolution in the reduction of circulating field virus can be followed at herd and/or population level by serological monitoring for antibodies against gE, using commercially available enzyme-linked immunosorbent assays. To be successful, other measures besides the vaccination in itself are important, such as the proper use and administration of the vaccine, repeated boosters, prevention of introduction of gE-positive animals and restriction in the movement of animals from gE-positive herds. When pockets of infection remain, intensifying the vaccination may be needed. Culling of remaining gE-positive animals, particularly breeders, is usually necessary. Some European Union (EU) member states have become ADV-free using this approach. Others are still working at it. The success is often dependent on whether or not a good discipline exists. The disease situation in the different EU member states is described. In ADV-free regions with dense swine populations at risk, it is advisable not to stop the vaccination too soon, particularly when the infection status in neighbouring countries or trade partners is not equally good.
Animals↗
Cell culture propagation modifies the African swine fever virus replication phenotype in macrophages and generates viral subpopulations differing in protein p54.
We have detected 86 African swine fever (ASF) virus-induced proteins in infected pig macrophages by two-dimensional electrophoresis. No differences among protein patterns of wild-type viruses could be observed by this methodology. However, during cell culture adaptation and propagation we have characterized changes in the molecular weight of the ASF virus specified protein p54, which show direct correlation with both size and number of viral subpopulation variants generated during cell culture propagation. Passages in culture appear to select for viral subpopulations that specify p54 proteins with higher molecular weights than the wild-type virus. The virus propagation in cell culture also affected its replication phenotype in pig macrophages decreasing the viral titers in these cells between passage 44 and 81. Nevertheless, the changes observed in p54 did not imply differences in biological properties, such as infectivity, virulence or host cell range among viral clones isolated, each one specifying for only one p54 form with different molecular weight. This protein becomes then a valuable quantification marker to follow evolution and generation of ASF virus diversity in vitro.
African Swine Fever↗
Primary structure of influenza virus genome regions coding for polypeptides from the major antigenic sites of H3 hemagglutinin.
Nucleotide sequences for some regions of the hemagglutinin (HA) gene of influenza virus A/Leningrad/385/80 (H3N2) were analyzed. A double-stranded complementary DNA was synthesized on the influenza genome RNA in the presence of synthetic oligodeoxyribonucleotides A GCAAAAGCAGG and A GTAGAAACAAG and inserted into the Pst I-site of the pBR322 plasmid through G-C-tailing. Nucleotide sequences were determined by a solid phase modification of the Maxam and Gilbert procedure. A comparison of our data with those for influenza virus A/Bangkok/1/79, which is the nearest sequenced prototype of the strain investigated, revealed only two base changes in the variable region of the HA gene. One of them was accompanied by a change in the coded amino acid (Asp53----Tyr) located in the antigenic site E of the HA glycoprotein. There also were some point mutations in the constant region of the gene. The results obtained are discussed in terms of the evolution of "Hong Kong" influenza viruses during their circulation.
Antigens, Viral↗
Mechanisms of spiroplasma genome variation associated with SpV1-like viral DNA inferred from sequence comparisons.
Genomes of Spiroplasma citri strains have rearranged frequently during their evolution, partly due to multiple integrated sequences of spiroplasma viruses. To understand better the role of viral sequences in genome evolution, we examined available nucleotide sequences of viruslike elements in the S. citri chromosome. Comparison of integrated and nonintegrated sequences of spiroplasma virus SpV1-C74 DNA suggested that it is an encapsidated form of the circular transposition intermediate belonging to an insertion sequence (IS3) family member. One SpV1-C74 viral DNA fragment was identified as interrupting the remains of a DNA adenine modification methylase gene. A viral DNA insertion of SpV1-R8A2 B DNA had hallmarks of having suffered an internal deletion by a site-specific recombination system. Homologous recombination likely was responsible for several deletions within viral DNA. A homologous recombination event was inferred between part of a viral DNA insertion and a similar chromosomal sequence. Dispersed sequences from SpV1-like C4 open reading frames (ORFs) were identified as involved in a complex deletion-inversion event. Thus, SpV1-like sequences likely have altered spiroplasma genomes by inserting within active genes, destroying their function, by providing targets for site-specific recombination, by mediating deletions of sequences adjacent to their integration sites, and by providing targets for homologous recombination, leading to inversions.
Amino Acid Sequence↗
Serological and biochemical analysis of foot-and-mouth disease virus (serotype C3) isolated in Argentina between 1981 and 1986.
The evolution in the field is described for foot-and-mouth disease viruses belonging to serotype C3 in Argentina between 1981 and 1986. During 1981 and 1982 only three isolations of this serotype took place, which showed minor serological and biochemical variations from the prototype strain C3 Resende-Brasil/55. At the beginning of 1983 an outbreak was detected in a restricted geographical region caused by strains which had important serological and biochemical differences from the prototype strain. However, revaccination of the animals with the available commercial vaccine was sufficient to control the disease. During 1984 and up to 1986, a new outbreak of the same serotype took place in an extended geographical region of Argentina. During this outbreak, two field strains were isolated, studied and later included in the vaccine. One of them, strain C84, was a serological variant of the prototype strain and its inclusion in the vaccine had only a limited effect in controlling the disease. Inclusion of the other representative strain, C85, together with virus C84 finally reduced the number of outbreaks to the usual number reported.
Animals↗