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Evolution of structural proteins of feline immunodeficiency virus: molecular epidemiology and evidence of selection for change.

The DNA sequences of structural genes of several U.K. and European isolates of feline immunodeficiency virus (FIV) were determined and compared with those of other worldwide isolates. Phylogenetic analyses of both gag and env sequences demonstrate that a Japanese isolate represents a distinct sequence subgroup, with corrected amino acid distances to the other isolates averaging 23% in env and 8% in gag. Analysis also reveals that an evolutionary radiation of FIV occurred with many isolates diverging at approximately the same time, and that although isolates from similar geographical sources often cluster together, there is evidence of more than one origin for FIV in the U.K., The Netherlands and Italy. Estimation of the numbers of silent and replacement nucleotide substitutions indicates the presence of constraints against amino acid changes in gag and conserved regions of env but suggests that positive selection for protein sequence changes operates in variable regions of env. The possible immunological forces underlying these changes are discussed.

Amino Acid Sequence↗

[Virus in sheep's skin].

In a double sense, the ovine gamma herpesvirus type 2 (OvHV-2) is a virus in sheep's skin. Not only is it present world wide in all sheep breeds but also it causes malignant catarrhal fever (MCF) in cattle pigs, elk, and bison. OvHV-2 cannot be propagated in cell culture. Therefore, new results from OvHV-2 research are based on molecular techniques and may be summarized as follows. OvHV-2 is transmitted by respiratory routes as well as by sexual intercourse. Lambs are infected within the first few months of life. Leucocytes, primarily latently infected lymphocytes, are responsible for disseminating the virus over the entire organism. On rare occasions, virus particles could be visualized by electron microscopy in explanted lymphocyte cultures. Structural antigens were detected by immunohistology in M-cells of diseased rabbits. Immunologically and cell biologically active genes have been detected on the viral genome.The products arising from those are thought to fine balance, the number of latently infected cells in sheep and to keep them alive without causing harm. Thus, it seems that this balance has been found through co-evolution, favoring both virus and natural host. In contrast, other host species that were exclude from the process of co-evolution, are bound to fall from MCF.

Animals↗

Nonreplicative homologous RNA recombination: promiscuous joining of RNA pieces?

Biologically important joining of RNA pieces in cells, as exemplified by splicing and some classes of RNA editing, is posttranscriptional, whereas in RNA viruses it is generally believed to occur during viral RNA polymerase-dependent RNA synthesis. Here, we demonstrate the assembly of precise genome of an RNA virus (poliovirus) from its cotransfected fragments, which does not require specific RNA sequences, takes place before generation of the viral RNA polymerase, and occurs in different ways: Apparently unrestricted ligation of the terminal nucleotides, joining of any one of the two entire fragments with the relevant internal nucleotide of its partner, or internal crossovers within the overlapping sequence. Incorporation of the entire 5' or 3' partners into the recombinant RNA is activated by the presence of terminal 3'-phosphate and 5'-OH, respectively. Such postreplicative reactions, fundamentally differing from the known site-specific and structurally demanding cellular RNA rearrangements, might contribute to the origin and evolution of RNA viruses and could generate new RNA species during all stages of biological evolution.

3' Untranslated Regions↗

Evolution and characterization of tetraonine endogenous retrovirus: a new virus related to avian sarcoma and leukosis viruses.

In a previous study, we found avian sarcoma and leukosis virus (ASLV) gag genes in 19 species of birds in the order Galliformes including all grouse and ptarmigan (Tetraoninae) surveyed. Our data suggested that retroviruses had been transmitted horizontally among some host species. To further investigate these elements, we sequenced a replication-defective retrovirus, here named tetraonine endogenous retrovirus (TERV), from Bonasa umbellus (ruffed grouse). This is the first report of a complete, replication-defective ASLV provirus sequence from any bird other than the domestic chicken. We found a replication-defective proviral sequence consisting of putative Gag and Env proteins flanked by long terminal repeats. Reverse transcription-PCR analysis showed that retroviral gag sequences closely related to TERV are transcribed, supporting the hypothesis that TERV is an active endogenous retrovirus. Phylogenetic analyses suggest that TERV may have arisen via recombination between different retroviral lineages infecting birds. Southern blotting using gag probes showed that TERV occurs in tetraonines but not in chickens or ducks, suggesting that integration occurred after the earliest phasianid divergences but prior to the radiation of tetraonine birds.

Amino Acid Sequence↗

Diversity, divergence, and evolution of cell-free human immunodeficiency virus type 1 in vaginal secretions and blood of chronically infected women: associations with immune status.

Most human immunodeficiency virus type 1 (HIV-1) infections are believed to be the result of exposure to the virus in genital secretions. However, prevention and therapeutic strategies are usually based on characterizations of HIV-1 in blood. To understand better the dynamics between HIV-1 quasispecies in the genital tract and blood, we performed heteroduplex assays on amplified env products from cell-free viral RNA in paired vaginal secretion (VS) and blood plasma (BP) samples of 14 women followed for 1.5 to 3.5 years. Diversity and divergence were less in VS than in BP (P = 0.03 and P < 0.01, respectively), and divergence at both sites was correlated with blood CD4(+) cell levels (VS, P = 0.05; BP, P = 0.01). Evolution of quasispecies was observed in 58% of the women; the loss or gain of quasispecies in VS or BP was always accompanied by such changes at the other site. In addition, sustained compartmentalization of quasispecies in VS was found for four women, even as CD4(+) cell levels decreased to low levels (<50 cells/microl). Quasispecies changes over time were associated with fluctuations in CD4(+) cell levels; concordant increases or decreases in VS and BP divergence had greater CD4(+) cell level changes than intervals with discordant changes (P = 0.05), and women with evolving quasispecies had greater decreases in CD4(+) cell levels compared to that for women who maintained the same quasispecies (P < 0.05). Thus, diversity, divergence, and evolution of cell-free HIV-1 in VS can be different from that in BP, and dynamics between their respective quasispecies are associated with changes in CD4(+) cell levels.

Adolescent↗

Heterogeneity in evolutive patterns of inbred mice infected with a cloned substrain of mouse hepatitis virus type 3.

F1 hybrid mice, resulting from a cross between a susceptible and a resistant parent, were infected with a cloned substrain of mouse hepatitis virus type 3 (MHV3). Results showed various evolutive patterns ranging from fulminant hepatitis to persistent infection and excluded virus variation as an explanation for different disease types. Since host resistance to MHV3 has been previously shown to be under the genetic influence of 1 or 2 genes only rather than a polygenic phenomenon, these results strongly suggest that nongenetic factors play a major role in the determination of evolutive patterns.

Acute Disease↗

A model of the virus-type strategy in the early stage of encoded molecular evolution.

Recent advances in evolutionary molecular engineering have revealed that the essential nature of a "virus" in the evolutionary aspect is its bonding strategy for assignment of the phenotype to its genotype. Based on the definition of "virus"-type and "cell"-type of the assignment strategy, we propose a virus-early/cell-late model of the history of life. The first encoded protein is assumed to be a cofactor of replication ribozyme in the RNA world and to be bound to its genetic RNA. As such a virus-type strategy could introduce the Darwinian selection process into the hypercycle with translation, a hypercycle with virus-like members could make the replicase protein and the translation system gradually evolve together out of the RNA world without a proto-cell. Moreover, they could evolve much faster by this virus-type strategy than by a primitive cellular organism.

Animals↗

Application of a monoclonal antibody recognizing protein p30 to detect African swine fever virus-infected cells in peripheral blood.

Monoclonal antibody (MAb) 174F11.8 recognizes an epitope of the African swine fever (ASF) virus-induced protein, p30, a protein expressed on the plasma membrane of infected cells. This MAb has been used to analyze infected cell populations in peripheral blood of experimentally inoculated pigs with a virulent or attenuated ASF virus. Flow cytometric analysis of peripheral blood at different days postinfection using this MAb, showed expression of p30 mainly in the monocyte/macrophage cell lineage. Additionally, a small percentage of granulocytes also expressed p30 during infection. This methodology allowed the quantification of fluctuations in the pool of infected monocyte/macrophage cells in the inoculated pigs, maximum percentages ranging between 6 and 31%. Significant differences in the percentages of cell populations expressing p30 were not found between virulent or attenuated virus infection. However, a 2- to 4-day delay in the maximum percentage of cells expressing p30 was observed during infection with the attenuated virus when compared to virulent virus infection. Percentages of infected cells detected by the expression of p30 and viral titres obtained in peripheral blood showed positive correlation. Consequently, MAb 174F11.8 constitutes a marker to follow evolution of ASF virus infection, allowing quantification of percentages of infected cells in peripheral blood.

African Swine Fever↗

Viral hepatitis and primates: historical and molecular analysis of human and nonhuman primate hepatitis A, B, and the GB-related viruses.

The hepatitis viruses have long been assumed to be highly host-specific, with infection of other nonhuman primates occurring due to inoculation with, or exposure to, human viruses. This paradigm has slowly changed over the last 10 years, as mounting data has revealed nonhuman primate equivalents of hepatitis A virus, hepatitis B virus, and the hepatitis C-related viruses GBV-C and GBV-A. This review summarizes the historical and molecular information for each of these groups and highlights the impact of these nonhuman primate hepatitis viruses on our understanding of the evolution of each of these viruses.

Animals↗

Evolution and biological characterization of human immunodeficiency virus type 1 subtype E gp120 V3 sequences following horizontal and vertical virus transmission in a single family.

It has been suggested that immune-pressure-mediated positive selection operates to maintain the antigenic polymorphism on the third variable (V3) loop of the gp120 of human immunodeficiency virus type 1 (HIV-1). Here we present evidence, on the basis of sequencing 147 independently cloned env C2/V3 segments from a single family (father, mother, and their child), that the intensity of positive selection is related to the V3 lineage. Phylogenetic analysis and amino acid comparison of env C2/V3 and gag p17/24 regions indicated that a single HIV-1 subtype E source had infected the family. The analyses of unique env C2/V3 clones revealed that two V3 lineage groups had evolved in the parents. Group 1 was maintained with low variation in all three family members regardless of the clinical state or the length of infection, whereas group 2 was only present in symptomatic individuals and was more positively charged and diverse than group 1. Only virus isolates carrying the group 2 V3 sequences infected and induced syncytia in MT2 cells, a transformed CD4(+)-T-cell line. A statistically significant excess of nonsynonymous substitutions versus synonymous substitutions was demonstrated only for the group 2 V3 region. The data suggest that HIV-1 variants, possessing the more homogeneous group 1 V3 element and exhibiting the non-syncytium-inducing phenotype, persist in infected individuals independent of clinical status and appear to be more resistant to positive selection pressure.

Amino Acid Sequence↗

Evolution of lamivudine-resistant hepatitis B virus and HIV-1 in co-infected individuals: an analysis of the CAESAR study. CAESAR co-ordinating committee.

OBJECTIVES: Lamivudine has potent activity against HIV-1 and hepatitis B virus (HBV). Co-infection with these two viruses is common, and this may therefore influence the choice of antiretroviral therapies. A cohort of co-infected patients treated with lamivudine were studied in order to evaluate the differential effects of lamivudine on the two viral populations within the same individual after 44-52 weeks of therapy. DESIGN AND METHODS: Retrospective virological analysis of an HIV-1/HBV co-infected lamivudine cohort derived from a randomized, placebo-controlled study of lamivudine in HIV infection, the CAESAR study. RESULTS: Five of thirteen patients with HBV viral load > 10,000 copies/ml after 44-52 weeks of lamivudine therapy had genotypic drug resistance. Four of these five had a rebound of viral replication over the period of study and in one case this was associated with an alanine transaminase serum elevation. Ten of the thirteen patients had a 44-52 week HIV viral load > 1000 copies/ml, all of whom also had HIV reverse transcriptase M184V or M184I mutations. CONCLUSIONS: Extrapolating these results to the population yields an estimated 1-year incidence of drug-resistant HBV of at least 14% in lamivudine-treated HIV-1/HBV co-infected patients. The clinical and virological benefit of HBV lamivudine monotherapy in co-infected patients should be balanced against the potential for emergence of drug resistance. Further, these data suggest that the determinants of HIV and HBV drug resistance are different and that parallel evolution, rather than co-evolution of HBV and HIV-1 in co-infected individuals occurs.

CD4 Lymphocyte Count↗

Classification of Marek's disease viruses according to pathotype: philosophy and methodology.

The concept of pathotype in Marek's disease (MD) probably dates from the recognition of a more virulent form of the disease in the late 1950s (Benton & Cover, 1957). Distinctions between MD virus strains were further expanded with the description of the vv pathotype in the early 1980s and of the vv+ pathotype in the 1990s. Pathotype designations reflect important biological properties that correlate with the break-through of vaccinal immunity in the field. However, pathotyping methods applied by various laboratories have not been uniform, preventing critical comparison of results. Better uniformity of pathotyping procedures is desirable.The Avian Disease and Oncology Laboratory (ADOL) method is based on induction of lymphoproliferative lesions in vaccinated chickens. This method has been used to pathotype more than 45 isolates and is the basis for the current pathotype classification of MD virus strains. Its limitations include requirements for a specific type of chickens (15x7 ab+), large numbers of animals, and a statistical method to compare lesion responses to those of JM/102W and Md5 control strains. Because of these limitations, it has not been and is not likely to be used in other laboratories. Comparability in pathotyping can be improved by the comparison of field isolates with standard prototype strains such as JM/102W, Md5 and 648A (American Type Culture Collection) or their equivalents. Data may be generated by different in vivo procedures that measure tumour induction, neurological disease (both neoplastic and non-neoplastic lesions), or solely non-neoplastic criteria (such as lymphoid organ weights or virus replication). Methods based on neoplastic criteria, especially when generated in MD-immunized chickens, will probably correlate most closely with that of the ADOL method and be most relevant to evolution of MD virus in the field. Based on data from several trials, a modification of the ADOL method that utilizes fewer chickens and can be conducted with commercial specific pathogen free strains is proposed. The modified method is based on "best fit" comparisons with prototype strains, and is expected to provide results generally comparable with the original method. A variety of other alternative criteria (see earlier) are also evaluated both for primary pathotyping and as adjuncts to other pathotyping methods. Advantages and disadvantages of alternative methods are presented.

Animals↗

Phylogenetic insights into the evolution of parasitism in hymenoptera.

The Hymenoptera are one of the four megadiverse orders of insects, with over 100000 described species and several times this number still waiting to be described. A major part of this diverse group is formed of large lineages of parasitoid wasps. Some of these lineages have in turn given rise to subgroups that have gone on to diversify into other lifestyles, such as gall-forming on, and pollination of, plants, as well as a broad array of food-collecting behaviors associated with social living in colonies. Thus, the Hymenoptera demonstrate the large evolutionary potential of parasitism as a lifestyle, in contrast to early assertions that parasitism tends to lead to evolutionary 'dead ends' driven by overspecialization. Phylogenetic approaches have already led to a number of important insights into the evolution of parasitism in Hymenoptera. A series of examples are discussed in this review, including the origin of parasitism in the order, the development of koinobiosis in some groups, coevolution with symbiotic viruses, and the evolution in some groups away from parasitism and into such habits as gall formation, pollination of figs, nest building and sociality. The potential for comparative analysis of hymenopteran habits is large, but progress is still in its early stages due to the paucity of available well-supported phylogenies, and the still limited accumulation of basic biological data for many taxa.

Animals↗

Reassortment of human rotaviruses carrying rearranged genomes with bovine rotavirus.

Rotaviruses isolated from chronically infected immunodeficient children were previously shown to contain RNA yielding abnormal migration profiles on gels: normal RNA segments were lost or decreased in concentration, and additional bands of dsRNA were found which were derived (rearranged) from genome segments of lower molecular weight by concatemer formation. These viruses grew very slowly during passage in secondary rhesus monkey kidney cells. Upon superinfection with the tissue culture-adapted UK Compton strain of bovine rotavirus (BRV) extensive genome reassortment occurred. Clones with the following reassorted genome patterns were isolated: (i) RNA segments 5 or 6 of BRV were replaced by the corresponding RNA segments of human rotavirus; (ii) RNA segments 9 or 11 of BRV were replaced by different rearranged bands of RNA of human rotavirus; (iii) reassortants were observed containing more than one segment/rearranged band of human rotavirus RNA in different combinations. The reassortant viruses possessed functional proteins coded for by the genome segments and/or by rearranged bands of RNA of the human rotaviruses. Rearrangement of parts of the rotavirus genome may be a mechanism of evolution of these viruses.

Animals↗

Avian reticuloendotheliosis viruses: evolutionary linkage with mammalian type C retroviruses.

Reticuloendotheliosis viruses have been shown to be causative of tumors in a variety of avian species. The major structural protein of these non-genetically transmitted viruses is demonstrated to possess antigenic determinants common to those of all known mammalian type C viruses. These findings establish a mammalian origin for this oncogenic avian retrovirus group. None of the known mammalian type C virus groups demonstrated a closer immunological relationship to avian reticuloendotheliosis viruses. These results suggest that reticuloendotheliosis viruses have been non-genetically transmitted for a long period of evolution or that these viruses may have arisen by relatively recent infection of birds with an as yet undiscovered mammalian type C retrovirus.

Antigens, Viral↗

Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts.

Although polymorphisms of chemokine genes (SDF1, stromal cell-derived factor-1 and RANTES, regulated on activation, normal T cell expressed and secreted) and chemokine-receptor genes (CCR5, CCR2, CX(3)CR1) were shown to be associated with sensitivity to HIV infection and untreated HIV disease progression, their association with the response to highly active antiretroviral therapy (HAART) remains unclear. To explore the possible influence of such polymorphisms on the evolution of AIDS in treated patients, we have studied SDF1-3'A, CCR5Delta32, CCR2-64I, CX(3)CR1-249I, and CX(3)CR1-280M polymorphisms in HIV-infected patients under HAART (n = 169). We studied the evolution of plasma virus load and peripheral T lymphocyte counts in these patients up to 3 years after the initiation of HAART. We observed that some of the genetic polymorphisms studied had an impact on the evolution of these two parameters. After 1 year of HAART, patients with a virological response (undetectable plasma HIV-1 RNA) have a higher frequency of the homozygous SDF1-3'A genotype than other patients (p = 0.005). Similarly, patients with a CD4 increase of over 200/mm(3) from baseline after 1 year of HAART display higher frequencies of homozygous SDF1-3'A (p = 0.035) and homozygous CX(3)CR1-280M genotypes (p = 0.04) than other patients. Moreover, we showed that the CX(3)CR1- 280M allele was associated with higher peripheral CD4+ T cell counts not only in HIV+ patients but also in healthy controls (p = 0.003).

Adult↗