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[Laryngeal tuberculosis: considerations on the most recent clinical and epidemiological data and presentation of a case report].

According to the "Global Tuberculosis Control" performed in 1999--the third complete, international, global report on tuberculosis infection--173 countries reported their infection data to the WHO; of these countries 102 met the criteria for "DOTS programs" at the end of 1997. The DOTS programs are the only control strategy able to produce a cure rate of 85%. Both at the national and international (Centers of Disease Control) levels, guidelines have been drawn up to improve and coordinate the fight against tuberculosis. New indicators and methods of analysis should be developed to quantify the full impact on the control of infection transmission, incidence, prevalence, mortality and prevention of drug resistance. In addition, two significant world-wide events have affected the increase morbidity rate seen in the last decade in the more highly industrial countries: immigration from countries outside the European Community and HIV infection. The tuberculosis infection worsens the evolution of HIV, facilitating viral replication. In the present work the authors discuss the most recent epidemiological data regarding tuberculosis infection and review the Literature on the primary laryngeal location of the disease. Then they present a clinical case which recently came under observation. This case is a typical example of the clinical picture of the laryngeal tuberculosis seen today. It must not be forgotten that in recent years there has been an increase in morbidity in Italy, in both the pulmonary and extrapulmonary forms of the disease, although in our country the problem of delayed or incomplete reporting is quite widespread. The data show that the age ranges with the highest incidence of both pulmonary and extrapulmonary forms are the 25-35 and 60-70 year groups. Distribution by sex, on the hand, shows that the pulmonary forms are most often seen in males while the extrapulmonary forms have practical the same frequency in both sexes. In recent years the clinical and morphological aspects of tubercular laryngitis have changed significantly from what they were before chemotherapy and the most common clinical form is pseudotumoral tuberculosis. This form requires a differential diagnosis to distinguish it from neoplasms because they present a similar objective picture and have no signs of simultaneous or previous pulmonary involvement.

Diagnosis, Differential↗

[Analysis of eleven isolated transfusion transmitted virus genotype].

OBJECTIVE: To analyze transfusion transmitted virus (TTV) genotype in hepatitis patients and healthy people. METHODS: DNA fragment of TTV was amplified by polymerase chain reaction with nested primers in eight patients with liver disease and three healthy persons. The nested PCR products were cloned and sequenced. RESULTS: A TTV DNA sequence of 222 bp (primer sequence excluded) was compared among the 11 subjects. The similarity between N22 and WH1, WH2, WH3, GZ1, GZ2, GZ3, SD2, SD3 was 97.0%, 97.0%, 98.0%, 98.0%, 95.0%, 95.0%, 94.6% and 95.5%, respectively. The similarity between TXO11 and GZ4, SD1, XJ1 was 98.0%, 98.0% and 95.0%, respectively. CONCLUSION: According to Okamoto's method, the eleven TTV clones are classified into two subtypes: genotype 1a and 1b.

Base Sequence↗

[The histological lesions of chronic hepatitis C as predicting factors of sustained response to the treatment with interferon].

BACKGROUND: Although many studies have been implemented in order to determine the pre-treatment factors that can predict patients' response to interferon (IFN) therapy, it is not yet clear whether characteristic histologic abnormalities in chronic hepatitis C can predict such response. AIMS: The aim of this study were to evaluate, in patients with chronic hepatitis C, (i) the predictive value of histologic lesions for the sustained response to IFN therapy (ii) other pre-treatment (epidemiological and analytical) factors known to be predictive of response. PATIENTS AND METHODS: Sustained response was retrospectively evaluated in two hundred one patients who had been treated with IFN for at least 3 months in four different hospitals from Castilla y León. The following histological parameters were studied as predictors of response: histological diagnosis, Knodell index, grading and stage, characteristic histologic lesions of HCV infection. Epidemiological and analytical parameters were also evaluated. RESULTS: The rate of patient's sustained response to IFN treatment was 16%. None of the histological parameters was useful to predict this response. By univariate analysis, age, disease evolution time, mode of viral transmission, GGT, ferritin and viral genotype were associated with a sustained response. The most powerful, and only independent predictive factor, however, was the genotype (the response odds ratio was 8.6). CONCLUSIONS: Histological parameters do not predict the response to IFN treatment. Other factors (mainly the viral genotype) are associated with a higher response percentage, although no one is useful to decide which patients are going to respond.

Adult↗

Th1 and th2 responses, HIV-1 coreceptors, and HIV-1 infection.

The Th1/Th2 model provides an interesting paradigm for understanding several pathophysiological processes and possibly for developing new immunotherapeutical strategies. In HIV-1 infection the interaction between the type of HIV-1 strain and the pathway of the ongoing T-cell effector response, despite its complexity, may represent one of the crucial mechanisms in determining the outcome of virus infection. While the possibility of an HIV-1-driven Th1 to Th2 switch of the immune response is still debated, evidence is accumulating to suggest that cytokines produced during an immune response can contribute to promote a selective pressure toward the evolution of HIV-1 viral strains with different tropism. This article summarizes the results of our recent studies in which the expression of CCR5 and CXCR4 HIV-1 co-receptors, as well as the activity of R5- or X4- tropic strains of HIV-1 in different in vitro models of Th1/Th2 polarization was analyzed.

Acquired Immunodeficiency Syndrome↗

[Antiretroviral therapy].

The use of combinations of antiretroviral drugs can profoundly suppress HIV replication for prolonged periods and has substantially decreased AIDS-related morbidity and mortality. The optimal use of antiretroviral drugs remains a rapidly evolving field and numerous obstacles need to be addressed. Many regimens are associated with substantial toxicity, large pill burdens and high cost. In addition, it has become clear that currently available regimens cannot completely suppress HIV replication. Nevertheless, the goal of antiretroviral therapy remains the suppression of plasma viremia as much as possible for as long as possible. Additional goals of therapy include restoration and preservation of immune function, minimization of toxicity, to prevent the disruption of lifestyle and the emergence of drug-resistance virus strains. In some patients a sustained elevations in CD4 cell counts occur despite incomplete viral suppression during HAART. The optimal therapeutic approach in these patients is still unclear. If, as it is generally assumed, viral load determinations reflect ongoing viral replication, then the evolution of drug resistance might be expected. Thus, to prevent the emergence of multidrug resistance, also in these patients a change to a salvage therapy is a viable option.

Anti-HIV Agents↗

The clades of HIV: their origins and clinical significance.

It is over 20 years since the identification of HIV as the causative agent of AIDS. Despite the innovation and perseverance of biomedical researchers, HIV has cumulatively infected over 60 million individuals and caused the deaths of over 28 million, the majority in the developing world. There is perhaps no greater need in medical science than the development of more effective treatments for HIV and, ultimately, a protective vaccine. The spread of an extraordinary range of variants of HIV has implications for diagnosis and therapy. As the availability of antiretrovirals increases, data on the clinical response to treatment for non-B subtype infections has increasing relevance. Efficient targeting of the extreme genetic diversity of HIV-1, and an understanding of the processes underlying this, represents one of the major challenges in the control of this ongoing pandemic.

AIDS Vaccines↗

[Immunodeficiency viruses].

In the first part of this article some structural and biological aspects of the HIV viruses are presented, in our opinion among the most interesting ones, connected with the AIDS viruses. Viral infection and its evolution, particularly related with infection by HIV-2, will be presented later, in the light of our experience, obtained over several years work with African people infected by the virus. The AIDS viruses are complex retroviruses, with their own identity, but also with marked structural and biological resemblances to other retroviruses, equally pathogenical for animals. The lentivirinae subfamily to which the AIDS viruses belong includes other agents, usually classified according to the host they infect. In this way, the lentiviruses of the primates contain in the same group, besides those of HIV-1 and HIV-2, viruses that infect monkeys such as SIVMAC, SIVAGM, SIVSMM, etc. The comparative study of molecular genetics and biology of human and animal retroviruses in recent years has permitted significant progress in the understanding of the possible mechanisms that lead to the Immunodepressive Acquired Syndrome that characterizes AIDS. The presence of a gene that deactivates the activated lymphocytes only present in the lentiviruses of the primates, as well as the known tropism of those viruses to CD4 lymphocytes, and not found in the other groups, are biological aspects that are pointed out. We also refer to other characteristics of HIVs such as the cytolytic and sincicial capacity of these viruses in lymphocyte culture. Finally we present an analysis of what we were able to observe in individuals infected by HIV-2 in their own and African habitat.

Acquired Immunodeficiency Syndrome↗

Primary structure of the gene coding for the haemagglutinin of influenza virus A/Leningrad/385/80(H3N2): detection of a point mutation responsible for the antigenic drift.

Primary structure of the gene coding for haemagglutinin (HA-gene) of influenza virus A/Leningrad/385/80(H2N2) isolated during the epidemics of influenza in Leningrad in 1980 was determined. The close relationship of HA gene of this virus to the corresponding gene of the virus A/Bangkok/1/79(H3N2) was confirmed. It was shown that a single mutation in an antigenic site (the change from isoleucine to leucine at position 51 of HA1 gene) caused an antigenic drift. One silent mutation was detected (nucleotide 428 of HA1 gene) which points at the relatedness of strains A/Leningrad/385/80 with A/Bangkok/2/79 and with other more recent strains. These data allowed to determine the position of the strain A/Leningrad/385/80 HA gene regarding to the evolutionary relationships of HA genes of influenza A (H3N2 subtype) viruses. The branch leading to the above-mentioned strain is supposed to start from a point common for strains isolated following A/Bangkok/1/79. The mutations of HA genes presented in this subgroup were analysed supporting the notion on limited evolutionary potential of the subtype H3N2 influenza viruses.

Amino Acid Sequence↗

Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection.

The proliferative response of PBMC to hepatitis B virus (HBV) envelope, core, and e Ag was analyzed prospectively in 21 patients with acute self-limited HBV infection and compared with the response of patients with chronic HBV infection and different levels of HBV replication (i.e., hepatitis e Ag (HBeAg)- or anti-HBe-positive) and liver damage (i.e., chronic active hepatitis or chronic asymptomatic carriers). Our results indicate that: 1) HBV-infected subjects who develop a self-limited acute hepatitis show a vigorous PBMC response to hepatitis B core Ag and HBeAg, as expression of T cell activation; 2) appearance of a detectable lymphocyte response to HBV nucleocapsid Ag is temporally associated with the clearance of HBV envelope Ag; 3) in patients with chronic HBV infection the level of T cell responsiveness to hepatitis B core Ag and to HBeAg is significantly lower than that observed during acute infection; 4) T cell sensitization to HBV envelope Ag in acute and chronic HBV infection is usually undetectable and when measurable is expressed transiently and at low levels. These results may reflect immune events of pathogenetic relevance with respect to evolution of disease and viral clearance.

Adult↗

Genome similarities between plant and animal RNA viruses.

Gene sequence comparisons and protein comparisons provide more and more evidence that evolutionary links exist between plant and animal RNA viruses, irrespective of whether they have an isometric or rod-shaped particle, or of whether they have a divided or non-divided genome. Although a phylogeny based on these molecular data cannot yet be constructed the results obtained so far shed a new light on the origin and evolution of RNA viruses and are important in terms of their taxonomy.

Biological Evolution↗

The molecular biology of the morbillivirus (measles) group.

The morbilliviruses are a closely related group of important human and animal pathogens. The best known members of the group are measles virus in man and canine distemper virus in dogs. The group also includes two other serious animal diseases, rinderpest or cattle plague and peste des petits ruminants in sheep and goats. The latter viruses are of great economic importance in Africa, Asia and the Middle East. Persistence of these viruses in some form is a possible mechanism whereby life-long immunity is conferred on an infected individual. In addition to the severe, often fatal, acute disease these viruses can, in rare cases, lead to a fatal chronic disease of the CNS. Molecular biological studies will be described which are beginning to elucidate their evolutionary relationships and to provide a basis for understanding the role of individual virus genes in pathogenesis.

Animals↗

[Evolution of the hemagglutinin gene of human influenza A virus H3 subtype].

An evolutional tree of human influenza viruses of the H3N2-subtype is suggested on the basis of combined published primary structures of the hemagglutinin HA1-subunit. Possible differences between natural and sequenced structures are discussed. A tendency to reversions in the course of antigenic draft within the subtype has been revealed to support the hypothesis of limited antigenic evolution within a single subtype.

Biological Evolution↗