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PubMedDate not supplied

[The interrelations of the human and avian influenza viruses A(H2) determined by the mathematical processing of data on the antigenic structure of their hemagglutinin].

Mathematical methods were used to analyse the data on the antigenic specificity of H2 subtype hemagglutinin of human and avian influenza A viruses. This approach allowed the evaluation of possible evolutional relationships in this little-studied group of viruses. Influenza A (H2) viruses isolated from birds in the USA were found to represent a sufficiently isolated group, whereas European avian strains (A/duck/Germany/1215/73, A/pintail duck/Primor'e/695/76, A/duck/Marseilles/46/76) were close to "human" viruses. The A/Leningrad/1468/65, A/laughing gull/New Jersey/75/85, and A/pintail duck/Alberta/2728/77 strains represent marked antigenic variants apparently rather far gone as a result of hemagglutinin drift.

Algorithms↗
PubMed2003

Predicting demographic group structures based on DNA sequence data.

The ability to infer relationships between groups of sequences, either by searching for their evolutionary history or by comparing their sequence similarity, can be a crucial step in hypothesis testing. Interpreting relationships of human immunodeficiency virus type 1 (HIV-1) sequences can be challenging because of their rapidly evolving genomes, but it may also lead to a better understanding of the underlying biology. Several studies have focused on the evolution of HIV-1, but there is little information to link sequence similarities and evolutionary histories of HIV-1 to the epidemiological information of the infected individual. Our goal was to correlate patterns of HIV-1 genetic diversity with epidemiological information, including risk and demographic factors. These correlations were then used to predict epidemiological information through analyzing short stretches of HIV-1 sequence. Using standard phylogenetic and phenetic techniques on 100 HIV-1 subtype B sequences, we were able to show some correlation between the viral sequences and the geographic area of infection and the risk of men who engage in sex with men. To help identify more subtle relationships between the viral sequences, the method of multidimensional scaling (MDS) was performed. That method identified statistically significant correlations between the viral sequences and the risk factors of men who engage in sex with men and individuals who engage in sex with injection drug users or use injection drugs themselves. Using tree construction, MDS, and newly developed likelihood assignment methods on the original 100 samples we sequenced, and also on a set of blinded samples, we were able to predict demographic/risk group membership at a rate statistically better than by chance alone. Such methods may make it possible to identify viral variants belonging to specific demographic groups by examining only a small portion of the HIV-1 genome. Such predictions of demographic epidemiology based on sequence information may become valuable in assigning different treatment regimens to infected individuals.

Adolescent↗
PubMed1979

Wild mouse RNA tumor viruses. A nongenetically transmitted virus group closely related to exogenous leukemia viruses of laboratory mouse strains.

Type-C RNA viruses isolated from wild mice are causative of naturally occurring neoplasia and neurologic diseases. Biochemical and immunologic characterization of this virus group revealed that amphotropic viruses isolated from wild mice trapped in separate geographical areas are indistinguishable, whereas amphotropic and ecotropic viruses naturally infecting the same animal are env gene variants. Molecular hybridization studies established that neither host range variant is endogenous to the Mus musculus genome, although each demonstrates partial nucleotide sequence homology. Wild mouse type-C viruses exhibited much closer molecular and antigenic relatedness to the exogenous virus subgroup (Friend-, Moloney-, and Rauscher-MuLV) than to prototype endogenous viruses isolated from laboratory mouse strains. The evidence indicates that exogenous mouse type-C viruses have been maintained in nature over a long period of evolution as a separate virus group, causative of tumors in mice by a mechanism solely involving their transmission as infectious agents.

Animal Population Groups↗
PubMed2003

[Necrotising histiocytic lymphadenitis in a patient with hypothyroidism. Aetiopatho-genesis and description of a rare clinical case].

Necrotising histiocytic lymphadenitis or Kikuchi-Fujimoto's disease is a rare benign disease characterised by cervical necrotising lymphadenopathy, high temperature, asthenia with complete restitutio ad integrum of the lymphnodal stations affected. A female patient A.B., aged 36, reached our clinic at the Medical Physiopathology Department of Rome's Umberto I Polyclinic in March 2001 for an endocrinological examination. The patient reported symptoms that led us to suspect hypothyroidism, a diagnosis that was later confirmed by haematochemical examinations and treated with Eutirox 100 g. After one month the patient returned to our clinic complaining of intensive asthenia, a feeling of general malaise, lack of appetite, serotin fever and painful laterocervical lymphadenopathy. Lymphnode biopsy gave an outcome of NHL. The histological finding suggested we should treat the case with anti-inflammatory drugs and after one month the symptoms had substantially retreated. To conclude, we suppose there is a possible relationship between the viral aetiology with chronic evolution of hypothyroidism in our patient and that of NHL.

Adult↗
PubMed2005

Partial sequence analysis of an atypical Turkish isolate provides further information on the evolutionary history of Plum pox virus (PPV).

A variety of techniques, such as typing with subgroup-specific monoclonal antibodies, restriction length polymorphism (RFLP) analysis or subgroup-specific RT-PCR are available for the discrimination of Plum pox virus (PPV) isolates. However, the existence of PPV isolates showing abnormal typing properties has been observed in the past [Candresse, T., Cambra, M., Dallot, S., Lanneau, M., Asensio, M., Gorris, M.T., Revers, F., Macquaire, G., Olmos, A., Boscia, D., Quiot J.B., Dunez, J., 1998. Comparison of monoclonal antibodies and polymerase chain reaction assays for the typing of isolates belonging to the D and M serotypes of Plum pox potyvirus. Phytopathology 88, 198-204.]. In an effort to understand the molecular mechanisms underlying such anomalous serological and molecular typing characteristics, partial 3' (1449 nt) and 5' (3706 nt) sequences have been determined for an atypical Turkish PPV isolate (Abricotier Turquie or Ab-Tk). The results obtained indicate that its unusual typing behaviour is caused by point mutations affecting key restriction sites and epitopes and confirm that this isolate represents a divergent member of the PPV-M subgroup. In addition, analysis of the partial Ab-Tk genomic sequences demonstrated that the 5' region of the genome of this isolate has a mosaic structure resulting from recombination event(s), shedding new light on the evolutionary history of Plum pox virus.

Antibodies, Monoclonal↗
PubMed1999

Viral RNA and evolved mutational robustness.

Many properties of organisms show great robustness against mutations. Whether this robustness is an evolved property or intrinsic to genetic systems is by and large unknown. An evolutionary origin of robustness would require a rethinking of key concepts in the field of molecular evolution, such as gene-specific neutral mutation rates, or the context-independence of deleterious mutations. We provide evidence that mutational robustness of the genome of RNA viruses to mutational changes in secondary structure has evolved. J. Exp. Zool. ( Mol. Dev. Evol.) 285:119-127, 1999.

Animals↗
PubMed1996

Consistent risk group-associated differences in human immunodeficiency virus type 1 vpr, vpu and V3 sequences despite independent evolution.

Human immunodeficiency virus 1 type vpr, vpu and V3 sequences from 15 homosexual men and 19 intravenous drug users in the Amsterdam Cohort studies were analysed. Previously, we reported that V3 domains of viruses from drug users are distinguishable from those of homosexual men on the basis of two silent mutations. Phylogenetic analysis of vpr, vpu and V3 shows that differences in all three regions correlate with risk group. Two positions in both vpr and vpu were found to differ significantly between the risk groups. The distinguishing positions were confirmed for sequences from 11 Scottish and four German samples. The three regions show relatively independent evolution patterns; they resulted in different phylogenies, the only stable clustering being that based on the risk group distinction. Pairwise differences between sequences of the genes were moderately correlated (around 0.30). Surprisingly, when only silent changes are counted, the correlations dropped almost to zero, indicating that the evolution towards independence was more advanced in the silent than in the non-silent positions. This suggests that selection at the amino acid level is not the primary driving force for the independent evolutionary behaviour of the genes. Recombination, combined with restrictions on certain amino acids because of epistatic interactions between the genes, could be an alternative explanation of this phenomenon.

Base Sequence↗
PubMedDate not supplied

[Role of stabilizing and splitting selection in evolution of of viruses from the Parvoviridae and Astroviridae families].

We had previously collected and analyzed, by phylogenetic methods, all genetic data available now for the Parvoviridae and Astroviridae families, which made it possible to define the evolutionary relations between the viruses as well as to depict a variety of events in the evolutionary history of the two families. The offered case study is dedicated to investigating the stabilizing and splitting selection types in the evolution of the discussed viral families. We analyzed the number of synonymous and non-synonymous nucleotide substitutions in the coding genomes' regions of the viruses. Finally, the stabilizing selection was shown to be a key factor in the evolution of parvoviruses and astroviruses.

Animals↗
PubMed1998

[Viremia levels of the chronic hepatitis c virus in HIV infected patients, clinical implications].

BACKGROUND: To know the clinical implications of the viremia level and its evolution in time of the hepatitis C virus (HCV) in patients with chronic hepatitis and infected with the Human Immunodeficiency Virus (HIV). PATIENTS AND METHODS: We have studied the viremia level of the HCV in a a 38 patients group with active chronic hepatitis and infected with the HIV, using a quantitative PCR technic (Amplicor HCV, Roche Diagnostics); we had histological data in 33 of these patients. In 20 patients was analyzed the evolution in time of the viremia level with two or three serialized measurements (20 and 10 patients respectively), throughout 7.5 and 14.8 months on the average. We have analyzed some aspects like the risky behaviors associated with transmission, the estimated time from the contagious, the degree of histological damage and the immunitary impairment. RESULTS: We have observed a tendency to present a higher viremia level (logarithmic expression) with longer evolution time from the infection (p = 0.08). The viral load had an inverse relation with the degree of histological fibrosis (Light fibrosis: 4.5 +/- 0.8 log vs Severe fibrosis: 3.7 +/- 0.8 log) (p < 0.01) and a direct relation with the Knodell histological activity index (HAI), only with those patients with a lower fibrosis degree (p < 0.01). There was no relation between the viremia level of the HCV and the degree of immunosuppression measured by the CD4 lymphocyte count, at least in those patients in which it was higher than 200/mm3. We have not observed relations between the viral load and the age or the transaminases level. The evolution in time of the viremia tended to rise from 3.7 +/- 1.3 to 4.5 +/- 0.9 log in 14.8 months on the average, although there were some cases with tendency to decrease. We have not observed relation between its increase/month and the degree of histological damage or the CD4 lymphocyte count. CONCLUSIONS: The viral load of the HCV in HIV-infected patients seems to have an inverse relation with the degree of liver fibrosis and direct relation with the histological activity when the fibrosis light and so it could indirectly inform us about the liver aggression. The degree of immunosuppression measured by the CD4 lymphocyte count, when these are > 200/mm3, doesn't seem to influence the viremia level of the HCV. The evolution of the viral load in time tend to rise although there could be some cases with intermittent or descending evolution, without these tendencies have any clinical implications.

HIV Infections↗
PubMed2006

Residual human immunodeficiency virus type 1 viremia in some patients on antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells.

Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1 persists in resting CD4+ T cells, and low residual levels of free virus are found in the plasma. Limited characterization of this residual viremia has been done because of the low number of virions per sample. Using intensive sampling, we analyzed residual viremia and compared these viruses to latent proviruses in resting CD4+ T cells in peripheral blood. For each patient, we found some viruses in the plasma that were identical to viruses in resting CD4+ T cells by pol gene sequencing. However, in a majority of patients, the most common viruses in the plasma were rarely found in resting CD4+ T cells even when the resting cell compartment was analyzed with assays that detect replication-competent viruses. Despite the large diversity of pol sequences in resting CD4+ T cells, the residual viremia was dominated by a homogeneous population of viruses with identical pol sequences. In the most extensively studied case, a predominant plasma sequence was also found in analysis of the env gene, and linkage by long-distance reverse transcriptase PCR established that these predominant plasma sequences represented a single predominant plasma virus clone. The predominant plasma clones were released for months to years without evident sequence change. Thus, in some patients on antiretroviral therapy, the major mechanism for residual viremia involves prolonged production of a small number of viral clones without evident evolution, possibly by cells other than circulating CD4+ T cells. The sequences have been deposited in GenBank. The accession numbers are DQ 391282 to DQ 391351 (for env) and DQ 391352 to DQ 392955 (for RT).

Antiretroviral Therapy, Highly Active↗
PubMed2002

Intrapatient diversity and its correlation with viral setpoint in human immunodeficiency virus type 1 CRF02_A/G-IbNG infection.

The human immunodeficiency virus type 1 (HIV-1) viral setpoint during the disease-free interval has been strongly associated with future risk of disease progression. An awareness of the correlation between viral setpoint and HIV-1 genetic evolution over time is important in the understanding of viral dynamics and infection. We examined genetic diversity in HIV-1 CRF02_A/G-IbNG-infected seroincident women in Dakar, Senegal; determined whether a viral setpoint kinetic pattern existed for CRF02_A/G-IbNG during the disease-free interval; and correlated viral load level and diversity. Samples were drawn during the disease-free interval from consenting CRF02_A/G-IbNG-infected, antiretroviral therapy-naïve female commercial sex workers in Dakar, Senegal. Based on sequential plasma RNA values, low and high viral setpoint groups were established. Intrapatient diversity and divergence over time was determined from earlier and later time point DNA samples from each person. Most individuals followed the viral setpoint paradigm. For each 1/-/log(10) copy/ml of plasma increase in viral load, intrapatient diversity increased by 1.4% (P = 0.028). A greater diversification rate was observed in the high viral setpoint group than in the low viral setpoint group (P = 0.01). Greater nucleotide (P = 0.015) and amino acid (P = 0.048) divergences and a greater nucleotide divergence rate (P = 0.03) were found in the high viral setpoint group. There was no difference between the groups in the ratio of the number of nonsynonymous substitutions per nonsynonymous site to the number of synonymous substitutions per synonymous site. The greater intrapatient diversity, divergence, and diversification rates observed in the high viral setpoint group supports the notion that diversity is driven by cycles of viral replication resulting in accumulated mutations. Recognizing diversity potential based on viral load levels in individuals may inform the design of vaccines and therapies.

Base Sequence↗
PubMedDate not supplied

HIV-1 evolution under pressure of protease inhibitors: climbing the stairs of viral fitness.

The human immunodeficiency virus (HIV-1) has evolved into a viral quasispecies with a high replication capacity or fitness. Antiretroviral drugs potently inhibit replication of the wild-type virus, but HIV-1 responds by selection of drug-resistant variants. Here we review, in brief, the evolution of resistance to protease inhibitors that is characterized by severe fitness losses and an abundance of subsequent repair strategies. The possibility to restrict HIV-1 fitness is discussed in relation to the control of HIV-1 pathogenesis.

Anti-HIV Agents↗