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At least 649 records · Page 36Linked to original sources
PubMed1999

Characterization of tobacco geminiviruses in the Old and New World.

Biological differences and molecular variability between six phenotypically distinct tobacco-infecting geminivirus isolates from southern Africa (Zimbabwe) and Mexico were investigated. Host range studies conducted with tobacco virus isolates ZIM H from Zimbabwe and MEX 15 and MEX 32 from Mexico indicated all had narrow host ranges restricted to the Solanaceae. Alignment of coat protein gene (CP) and common region (CR) sequences obtained by PCR, and phylogenetic analysis of the CP sequences indicated Zimbabwean isolates were distantly related to those from Mexico and that geographically proximal isolates shared their closest affinities with Old and New World geminiviruses, respectively. Zimbabwean isolates formed a distinct cluster of closely related variants (> 98% sequence identity) of the same species, while MEX 15 segregated independently from MEX 32, the former constituting a distinct species among New World geminiviruses, and the latter being a variant, Texas pepper virus-Chiapas isolate (TPV-CPS) with 95% sequence identity to TPV-TAM. Results collectively indicated a geographic basis for phylogenetic relationships rather than a specific affiliation with tobacco as a natural host. MEX 15 is provisionally described as a new begomovirus, tobacco apical stunt virus, TbASV, whose closest CP relative is cabbage leaf curl virus, and ZIM isolates are provisionally designated as tobacco leaf curl virus, TbLCV-ZIM, a new Eastern Hemisphere begomovirus, which has as its closest relative, chayote mosaic virus from Nigeria.

Base Sequence↗
PubMed2001

Molecular epidemiology of TT virus (TTV) and characterization of two novel TTV genotypes in Indonesia.

The prevalence of TT virus (TTV) DNA among 244 healthy individuals in 23 cities on 12 islands in Indonesia was determined by polymerase chain reaction (PCR) with primers derived from the coding region (N22), which can detect TTV DNA of genotypes 1-6. By N22 PCR, TTV DNA was detected in 102 (42%) individuals. The amplified PCR products were molecularly cloned and three clones each were subjected to sequence analysis. Three hundred one (98%) of the 306 TTV clones were classified into genotype 1, 2 or 3, and none into genotypes 4-6. The remaining five clones from two individuals (Kt-08 and Kt-10) on Kutai, Kalimantan Island, differed by >30% from known TTV isolates of all 21 genotypes and were tentatively classified into genotypes 22 and 23, respectively. Using primers specific for the new TTV genotype 22 or 23, TTV genotype 22 was detected significantly more frequently in Kutai than in the other 22 cities (41% vs. 5%, P < 0.001). TTV genotype 23 was restricted to Kutai (17% vs. 0%, P < 0.001), suggesting the indigenous nature of this genotype. Analysis of two TTV isolates (Kt-08F and Kt-10F) demonstrated the extreme diversity of TTV and the preservation of the genomic organization and transcription profile.

Adult↗
PubMed2005

Persistent nonallergic rhinosinusitis.

Nonallergic rhinitis is a complex of syndromes that are united by the absence of atopic, T(H)2 lymphocyte, immunoglobulin E (IgE)-mediated mechanisms. We propose a classification system based on the presence or absence of inflammatory granulocytes. Eosinophilic nonallergic rhinosinusitis may also be called chronic eosinophilic sinusitis syndromes (CESS) to help classify these disorders in which diverse mechanisms of eosinophil chemoattraction and survival predominate. Allergic fungal sinusitis, eosinophilic nasal polyps, aspirin sensitivity, and related disorders would fit in this category. Accumulation of neutrophils occurs in chronic infectious rhinosinusitis, foreign body reactions, and immunodeficiencies. More complex and variable combinations of leukocytes are found in Wegner's granulomatosis and related syndromes, and during the evolution of viral infections. The noninflammatory disorders can be divided by mechanism into hormonal; sympathetic dysfunction (including antihypertensive adrenergic drug therapy); cholinergic rhinitis; and nociceptive syndromes with hyperalgesia and other features (eg, the nonallergic rhinitis of chronic fatigue syndrome). Therapy based on the most likely pathophysiologic mechanism is anticipated to have the most success, but requires acceptance of the wide differential diagnosis of nonallergic rhinitis and rejection of the obsolete term of "vasomotor rhinitis."

Diagnosis, Differential↗
PubMed2006

Vaccine-derived poliovirus from long term excretors and the end game of polio eradication.

Seven cases of long-term poliovirus excretion in the UK and Ireland are reviewed in this paper. They include a rare case of long-term virus excretion by a healthy child recently found in Ireland and the case with the longest period of vaccine-derived poliovirus excretion by an immunodeficient individual ever known, 18 years. The evolution of viral properties such as antigenic structure, neurovirulence, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin vaccine strains were studied in detail. The relevance of these cases in the context of the global polio eradication initiative and the design of vaccination strategies for the last stages of eradication and the post-eradication era are discussed.

Child↗
PubMed2004

Predicting differential responses to structured treatment interruptions during HAART.

Highly active antiretroviral therapy (HAART) has been used clinically in various administration schemes for several years. However, due to the development of drug resistance, evolution of viral strains, serious side effects, and poor patient compliance, the combination of drugs used in HAART fails to effectively contain virus long term in a high proportion of patients. Our group and others have suggested a change to the usual regimen of continuous HAART through structured treatment interruptions (STIs). STIs may provide similar clinical benefits as continuous treatment such as reduced viral loads and reestablishment of CD4(+)T cells while allowing patients drug holidays. We explore the use of STIs using a previously published model that accurately represents CD4(+)T-cell counts and viral loads during both untreated HIV-1 infection and HAART therapy. We simulate the effects of different STI regimens including weekly and monthly interruptions together with variations in treatment initiation time. We predict that differential responses to STIs as observed in conflicting clinical trial data are impacted by the duration of the interruption, stage of infection at initiation of treatment, strength of the immune system in suppressing virus, or pre-therapy CD4(+)T-cell count or virus load. Our results indicate that dynamics occurring below the limit of detection (LOD) are influenced by these factors, and contribute to reemergence or suppression of virus during interruptions. Simulations predict that short-term viral suppression with varying interruption strategies does not guarantee long-term clinical benefit.

Antiretroviral Therapy, Highly Active↗
PubMed2006

Prevalent HBV genotypes and subtypes in a South Indian population.

BACKGROUND: Genotypes or genetic subtypes describe genetically related strains and have been described for viruses belonging to several different families. The eight major genotypes of hepatitis B virus (HBV) have distinct geographic distribution. Recent studies suggest possible pathogenic and therapeutic differences among HBV genotypes. OBJECTIVES: To evaluate the HBV genotypes of 85 samples by RFLP analysis and sequence the desired region to look for variations and identify the subtypes of the surface region. STUDY DESIGN: We studied 85 patients with HBV in order to identify the most prevalent genotype and subtype. Patients with HBV-related liver disease attending the Department of Gastroenterology at Owaisi Hospital and Research Centre were studied. RESULTS AND CONCLUSIONS: Genotype D1 was most prevalent. Genotyping was carried out by RFLP analysis and confirmed by sequencing. Nucleotide sequences showed significant homology (96-97%) with the other genotypes that have been reported. Subtype ayw was the most prevalent subtype within the surface region. Construction of a phylogenetic tree incorporating these isolates and other published HBV sequences showed that the isolates are derived from the same evolutionary tree. The study adds to our understanding of the genetic diversity of HBV and the geographical distribution of its subtypes, and will be useful for reconstructing the evolutionary history of HBV.

Adult↗
PubMed2005

Structural insights into the mechanisms of drug resistance in HIV-1 protease NL4-3.

The development of resistance to anti-retroviral drugs targeted against HIV is an increasing clinical problem in the treatment of HIV-1-infected individuals. Many patients develop drug-resistant strains of the virus after treatment with inhibitor cocktails (HAART therapy), which include multiple protease inhibitors. Therefore, it is imperative that we understand the mechanisms by which the viral proteins, in particular HIV-1 protease, develop resistance. We have determined the three-dimensional structure of HIV-1 protease NL4-3 in complex with the potent protease inhibitor TL-3 at 2.0 A resolution. We have also obtained the crystal structures of three mutant forms of NL4-3 protease containing one (V82A), three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point mutations in complex with TL-3. The three protease mutants arose sequentially under ex vivo selective pressure in the presence of TL-3, and exhibit fourfold, 11-fold, and 30-fold resistance to TL-3, respectively. This series of protease crystal structures offers insights into the biochemical and structural mechanisms by which the enzyme can overcome inhibition by TL-3 while recovering some of its native catalytic activity.

Crystallography, X-Ray↗
PubMed2004

Host nutritional status: the neglected virulence factor.

The emergence of new infectious diseases and old diseases with new pathogenic properties is a burgeoning worldwide problem. Severe acute respiratory syndrome (SARS) and acquired immune deficiency syndrome (AIDS) are just two of the most widely reported recent emerging infectious diseases. What are the factors that contribute to the rapid evolution of viral species? Various hypotheses have been proposed, all involving opportunities for virus spread (for example, agricultural practices, climate changes, rainforest clearing or air travel). However, the nutritional status of the host, until recently, has not been considered a contributing factor to the emergence of infectious disease. In this review, we show that host nutritional status can influence not only the host response to the pathogen, but can also influence the genetic make-up of the viral genome. This latter finding markedly changes our concept of host-pathogen interactions and creates a new paradigm for the study of such phenomena.

Animals↗
PubMed2006

Minimization of genetic distances by the consensus, ancestral, and center-of-tree (COT) sequences for HIV-1 variants within an infected individual and the design of reagents to test immune reactivity.

Eliciting maximal immune responses to highly divergent viruses is a challenge and a focus in AIDS vaccine development. Another challenge is to identify the immune correlates of protective immunity. Recent AIDS vaccine design approaches attempt to use reconstructed centralized viral sequences that minimize genetic differences to circulating viruses. Using these approaches, we derive and analyze consensus (CON), ancestral (ANC), and center-of-tree (COT) sequences to represent intra-individual HIV-1 env variants encoding a range of diversities and phylogenetic structures. Each reconstructed sequence significantly minimized genetic distances to extant sequences throughout the first 5 years of infection of an individual. Interestingly, ANC sequences diverged and were not significantly better than extant sequences in minimizing genetic distances at later stages of infection and disease, likely due to the development of a substantially asymmetric phylogeny. COT or CON sequences derived from autologous virus samplings may be useful for increasing the sensitivity of assessments of immune reactivity against HIV.

Amino Acid Sequence↗
PubMedDate not supplied

Epidemic keratoconjunctivitis caused by a new genotype of adenovirus type 8 (Ad8)-a chronological review of Ad8 in Southern Taiwan.

PURPOSE: To understand the pathogenic evolution of viral keratoconjunctivitis in Kaohsiung, Taiwan, a retrospective molecular and clinical analysis was conducted. METHODS: From January 1990 to December 1994, conjunctival swab samples from patients suspected of having viral conjunctivitis were collected for viral culture isolation, neutralization test (NT), and endonuclease cleavage analysis. Six restriction endonucleases, comprising HindIII, BamHI, SalI, SstI, SmaI, and PstI, were used for cleavage. Clinical examinations of patients were performed by two senior ophthalmologists. RESULTS: Twenty-one cases of a new genotype of adenovirus (Ad) type 8, designated as Ad8H, were discovered in the 27 detected adenovirus cases. The Ad8H has a distinct cleavage pattern, especially by HindIII and SalI. The Ad8H keratoconjunctivitis induced more subconjunctival hemorrhage (33.3%), keratitis (33.3%), and lymphadenopathy (85.7%) than other genotypes of Ad8 previously isolated in Kaohsiung, Taiwan. CONCLUSION: We have discovered a new genotype, Ad8H, which was prevalent as the main pathogen of the adenoviral keratoconjunctivitis in Kaohsiung, Taiwan from 1990 to 1994. Adenovirus type 8 is evolving into more genotypes with a trend towards more severe symptoms, including subconjunctival hemorrhage, keratitis, and lymphadenopathy.

Adenoviridae Infections↗
PubMed1995

Direct evaluation of the immunodominance of a major antigenic site of foot-and-mouth disease virus in a natural host.

The immunodominance of a major antigenic site of foot-to-mouth disease virus (FMDV) (serotype C; clone C-S8c1) in a natural host has been evaluated by serum immunoglobulin fractionation. Nineteen sera from either convalescent or vaccinated swine were fractionated by affinity chromatography using a synthetic peptide representing antigenic site A (the G-H loop of capsid protein VP1) coupled to a Sepharose matrix. Antigen-binding and neutralizing activities of serum fractions were quantitated. On average, about 57 or 27% of the virus-neutralizing activity (and about 35 or 12% of the virus-binding activity) from convalescent or vaccinated swine, respectively, corresponded to antibodies against site A. The results provide direct evidence of the important contribution of site A, and also of additional sites unrelated to site A, in the evoking of neutralizing antibodies by FMDV in a natural host. The proportion of antibodies directed to site A varied greatly among individual swine. Some animals evoked remarkably low levels of antibodies specific for site A although they were competent to raise antibodies against other antigenic sites of FMDV. Thus, the major antigenic site of FMDV shows heterogeneous dominance in a natural host. Possible implications for evolution of viral quasispecies are discussed.

Amino Acid Sequence↗
PubMed1997

Genotype of GB virus C/hepatitis G virus by molecular evolutionary analysis.

GB virus C/hepatitis G virus is a newly described virus. Classification of GB virus C/hepatitis G virus into genotypes has not been established. We analyzed nucleotide sequences within the 5' untranslated region of GB virus C/hepatitis G virus isolates and segregated these isolates into genotypes. Twenty serum samples with GB virus C/hepatitis G virus RNA from Australia, Cameroon, the Congo, Japan, Mongolia, and Bangladesh were studied. Reverse transcription and polymerase chain reaction were used to obtain GB virus C/hepatitis G virus RNA. After nucleotide sequences from the 5' untranslated region were determined, 68 nucleotide sequences, including 48 previously reported sequences, were analyzed by molecular evolutionary methods. The phylogenetic tree of the 5' untranslated region showed that all strains could be divided into three major genotypes, GB type (type 1), HG type (type 2), and Asian type (type 3). Bootstrap analysis indicated that the strains could be divided into three major genotypes but could not be further subdivided. Moreover, frequency histograms of pairwise distances between nucleotide sequences demonstrated only one peak. These result indicated that GB virus C/hepatitis G virus can be classified into three major genotypes, GB type (type 1), HG type (type 2), and Asian type (type 3), and should not be divided into minor subtypes.

Base Sequence↗
PubMed2003

[Anti-retroviral treatment interruptions in HIV-infected adults: causes, clinical, immunological and virological consequences].

INTRODUCTION: This retrospective study analyses causes as well as clinical, immunological and virological consequences of antiretroviral treatment interruptions (Ti) of more than 30 days in HIV-1 infected adults. METHODS: This causes were classified as related to drug toxicity, therapeutic or adherence failure. We studied therapeutic regimens before Ti and after treatment reinitiation (TR), clinical events related to Ti, CD4 cells and viral loads before Ti and at months 3, 6, 9, and 12 after TR. RESULTS: Out of 188 Ti analysed, 42.6% were related to therapeutic failure, 33.5% to drug toxicity, and 23.9% to adherence failure. Eight Aids defining clinical events were reported during Ti, in patients with low CD4 cells and high viral load (P < 0.05). Viral loads evolution after TR was better if Ti was related to treatment failure (P < 0.05), was prolonged (P < 0.05), and if CD4 cells were high before Ti and at TR (P < 0.05). Median CD4 cells was of 296/mm(3) at month 12 after TR vs 382 before Ti. CONCLUSIONS: Ti consequences are strongly related to CD4 cells, which decrease sharply during Ti, increasing Aids defining events probability. Prospective randomised clinical studies are needed to define usefulness of Ti.

Adult↗
PubMed2003

Complete nucleotide sequence and molecular characterization of two lytic Staphylococcus aureus phages: 44AHJD and P68.

The first complete nucleotide sequences of two lytic Staphylococcus aureus double stranded DNA phages, 44AHJD (16784 bp) and P68 (18227 bp), are reported. Both are small isometric phages, with short, non-contractile tails and a pre-neck appendage. Based on their morphology, their genome size, the similarity of the encoded gene products, the type of infection and on the possession of a type B DNA polymerase, 44AHJD and P68 are allocated to the order Caudovirales, family Podoviridae, genus 'phi29-like phages'. The genome of 44AHJD differs from that of P68 by a deletion spanning nucleotides 10091 to 11531 of the P68 genome. The electrophoretic analysis of the terminal DNA fragments of P68 DNA and P68 DNA protein complex suggested the presence of a terminal protein at either DNA end. In contrast to the lysis cassette of the phi29-like phages, which is located at the end of the late operon, the lysis cassette of 44AHJD and P68 is located within the structural genes.

Bacteriophages↗
PubMed2004

Comparison of sequential cytomegalovirus isolates in a patient with lymphoma and failing antiviral therapy.

BACKGROUND: Long-term anti-cytomegalovirus (CMV) treatments in immunocompromised patients are hampered by resistance to antiviral drugs. Longitudinal changes in the resistance genotype may depend on changes in selective pressure and the complexity of CMV isolates. OBJECTIVE: To evaluate longitudinal changes in the CMV resistance genotype and phenotype along with strain-specific variability in a patient with non-Hodgkin's lymphoma in whom successive anti-CMV treatments failed. STUDY DESIGN: The resistance phenotype and genotype of seven CMV isolates collected from one patient during a 2-year follow-up period were retrospectively analysed. In parallel, we used glycoprotein B (gB) genotyping, and a- and UL10-13-sequence analysis to study CMV interstrain variability. RESULTS: The patient was infected by at least three CMV strains plus variants of the parental strains. Resistance to ganciclovir, cidofovir and foscarnet was successively detected during the follow-up period. UL97 protein kinase changes responsible for resistance to ganciclovir were initially detected at residues 591 and 592, and then at position 594. Decreased sensitivity to foscarnet coincided with the appearance of amino acid substitution N495K in DNA polymerase, whereas cross-resistance to ganciclovir and cidofovir was due to the L501I substitution. CONCLUSIONS: The CMV isolates obtained from our patient were complex mixtures of strains. Changes in resistance genotypes depended on resistance selective pressure and were not linked to interstrain variation.

Aged↗
PubMed2002

Identification and characterization of the ecdysteroid UDP-glycosyltransferase gene of Epinotia aporema granulovirus.

The ecdysteroid UDP-glycosyltransferase (egt) gene of Epinotia aporema granulovirus (EpapGV) was cloned sequenced and its biological activity was assessed. It encodes a protein of 446 amino acids. Direct evidence that the cloned gene encodes an active EGT protein was obtained by transient expression assays in insect cells. The upstream untranslated region of the egt gene exhibits several consensus early promoter elements. Accordingly, the gene is expressed early upon infection of Epinotia aporema larvae and the EGT activity remains high until later times post infection. Sequence analyses indicate the presence of clusters of amino acid residues conserved among all the baculoviral EGTs, although their relation with proper protein folding, ligand binding and catalytic activity remain to be assessed. Phylogenetic trees consistently cluster the granulovirus EGTs separating them clearly from the nucleopolyhedroviruses.

Amino Acid Sequence↗