Silent codon positions in the A-rich HIV RNA genome that do not easily become A: Restrictions imposed by the RNA sequence and structure.

There is a strong evolutionary tendency of the human immunodeficiency virus (HIV) to accumulate A nucleotides in its RNA genome, resulting in a mere 40 per cent A count. This A bias is especially dominant for the so-called silent codon positions where any nucleotide can be present without changing the encoded protein. However, particular silent codon positions in HIV RNA refrain from becoming A, which became apparent upon genome analysis of many virus isolates.

Euclidean Distance Analysis Enables Nucleotide Skew Analysis in Viral Genomes.

Nucleotide skew analysis is a versatile method to study the nucleotide composition of RNA/DNA molecules, in particular to reveal characteristic sequence signatures. For instance, skew analysis of the nucleotide bias of several viral RNA genomes indicated that it is enriched in the unpaired, single-stranded genome regions, thus creating an even more striking virus-specific signature. The comparison of skew graphs for many virus isolates or families is difficult, time-consuming, and nonquantitative.

HIV-1 tolerates changes in A-count in a small segment of the pol gene.

Background: The HIV-1 RNA genome has a biased nucleotide composition with a surplus of As. Several hypotheses have been put forward to explain this striking phenomenon, but the A-count of the HIV-1 genome has thus far not been systematically manipulated. The reason for this reservation is the likelihood that known and unknown sequence motifs will be affected by such a massive mutational approach, thus resulting in replication-impaired virus mutants.

A Novel Astrovirus-Like RNA Virus Detected in Human Stool.

Several novel clades of astroviruses have recently been identified in human faecal samples. Here, we describe a novel astrovirus-like RNA virus detected in human stools, which we have tentatively named bastrovirus. The genome of this novel virus consists of 6,300 nucleotides organized in three open reading frames.

Impact of the biased nucleotide composition of viral RNA genomes on RNA structure and codon usage.

We are interested in the influence of nucleotide composition on the fundamental characteristics of the virus RNA genome. Most RNA viruses have genomes with a distinct nucleotide composition, e.g.

Nucleotide composition of the Zika virus RNA genome and its codon usage.

Background: RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and Central America and the Caribbean in 2015 and has recently been associated with microcephaly in newborns.

In silico prediction of ebolavirus RNA polymerase inhibition by specific combinations of approved nucleotide analogues.

Background And Objective: The urgency of ebolavirus drug development is obvious in light of the current local epidemic in Western Africa with high morbidity and a risk of wider spread. We present an in silico study as a first step to identify inhibitors of ebolavirus polymerase activity based on approved antiviral nucleotide analogues.

Study Design: Since a structure model of the ebolavirus polymerase is lacking, we performed combined homology and ab initio modeling and report a similarity to known polymerases of human enterovirus, bovine diarrhea virus and foot-and-mouth disease virus.

On the biased nucleotide composition of the human coronavirus RNA genome.

We investigated the nucleotide composition of the RNA genome of the six human coronaviruses. Some general coronavirus characteristics were apparent (e.g.

Specific mutations in the C-terminus domain of HBV surface antigen significantly correlate with low level of serum HBV-DNA in patients with chronic HBV infection.

Background: To define HBsAg-mutations correlated with different serum HBV-DNA levels in HBV chronically-infected drug-naive patients.

Methods: This study included 187 patients stratified into the following ranges of serum HBV-DNA:12-2000 IU/ml, 2000-100,000 IU/ml, and >100,000 IU/ml. HBsAg-mutations were associated with HBV-DNA levels by applying a Bayesian-Partitional-Model and Fisher-exact test.

Differential binding of tenofovir and adefovir to reverse transcriptase of hepatitis B virus.

Introduction: Resistance of the reverse transcriptase (RT) of hepatitis B virus (HBV) to the tenofovir nucleotide drug has not been observed since its introduction for treatment of hepatitis B virus (HBV) infection in 2008. In contrast, frequent viral breakthrough and resistance has been documented for adefovir. Our computational study addresses an inventory of the structural differences between these two nucleotide analogues and their binding sites and affinities to wildtype (wt) and mutant RT enzyme structures based on in silico modeling, in comparison with the natural nucleotide substrates.

On the nucleotide composition and structure of retroviral RNA genomes.

Retroviral RNA genomes display a rich variety in their nucleotide composition. For instance, the single-stranded RNA genome of human T cell leukemia virus (HTLV-1) is C-rich and G-poor and that of the human immunodeficiency virus (HIV-1) is A-rich and C-poor. Animal retroviruses add further variation to this unexplained, but many times remarkable virus-specific property.

Unexplained diarrhoea in HIV-1 infected individuals.

Background: Gastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. Although various enteric pathogens have been implicated, the aetiology of diarrhoea remains unexplained in a large proportion of HIV-1 infected patients. Our aim is to identify the cause of diarrhoea for patients that remain negative in routine diagnostics.

Identification of a new genotype of Torque Teno Mini virus.

Background: Although human torque teno viruses (TTVs) were first discovered in 1997, still many associated aspects are not clarified yet. The viruses reveal a remarkable heterogeneity and it is possible that some genotypes are more pathogenic than others. The identification of all genotypes is essential to confirm previous pathogenicity data, and an unbiased search for novel viruses is needed to identify TTVs that might be related to disease.

Anti-HBV treatment induces novel reverse transcriptase mutations with reflective effect on HBV S antigen.

Introduction: The identification of novel reverse-transcriptase (RT) drug-resistance mutations is critical in predicting the probability of success to anti-HBV treatment. Furthermore, due to HBV-RT/HBsAg gene-overlap, they can have an impact on HBsAg-detection and quantification.

Methods: 356 full-length HBV-RT sequences from 197 drug-naive patients and 159 patients experiencing virological-breakthrough to nucleoside/nucleotide-analogs (NUCs) were analyzed.

The A-nucleotide preference of HIV-1 in the context of its structured RNA genome.

A bipartition of HIV-1 RNA genome sequences into single- and double-stranded nucleotides is possible based on the secondary structure model of a complete 9 kb genome. Subsequent analysis revealed that the well-known lentiviral property of A-accumulation is profoundly present in single-stranded domains, yet absent in double-stranded domains. Mutational rate analysis by means of an unrestricted model of nucleotide substitution suggests the presence of an evolutionary equilibrium to preserve this biased nucleotide distribution.

The hepatitis B virus x protein inhibits thymine DNA glycosylase initiated base excision repair.

The hepatitis B virus (HBV) genome encodes the X protein (HBx), a ubiquitous transactivator that is required for HBV replication. Expression of the HBx protein has been associated with the development of HBV infection-related hepatocellular carcinoma (HCC). Previously, we generated a 3D structure of HBx by combined homology and ab initio in silico modelling.

Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection.

Occult HBV infection (OBI) is a threat for the safety of blood-supply, and has been associated with the onset of HBV-related hepatocellular carcinoma and lymphomagenesis. Nevertheless, genetic markers in HBsAg (particularly in D-genotype, the most common in Europe) significantly associated with OBI in vivo are missing. Thus, the goal of this study is to define: (i) prevalence and clinical profile of OBI among blood-donors; (ii) HBsAg-mutations associated with OBI; (iii) their impact on HBsAg-detection.

Protein X of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase.

Orthohepadnavirus (mammalian hosts) and avihepadnavirus (avian hosts) constitute the family of Hepadnaviridae and differ by their capability and inability for expression of protein X, respectively. Origin and functions of X are unclear. The evolutionary analysis at issue of X indicates that present strains of orthohepadnavirus started to diverge about 25,000 years ago, simultaneously with the onset of avihepadnavirus diversification.

Rooting human parechovirus evolution in time.

Background: The Picornaviridae family contains a number of important pathogenic viruses, among which the recently reclassified human parechoviruses (HPeVs). These viruses are widespread and can be grouped in several types. Understanding the evolutionary history of HPeV could answer questions such as how long the circulating lineages last shared a common ancestor and how the evolution of this viral species is shaped by its population dynamics.

Occult hepatitis B infection: an evolutionary scenario.

Background: Occult or latent hepatitis B virus (HBV) infection is defined as infection with detectable HBV DNA and undetectable surface antigen (HBsAg) in patients' blood. The cause of an overt HBV infection becoming an occult one is unknown. To gain insight into the mechanism of the development of occult infection, we compared the full-length HBV genome from a blood donor carrying an occult infection (d4) with global genotype D genomes.

Biodistribution and radiation dosimetry of 99mTc-HMPAO-labeled monocytes in patients with rheumatoid arthritis.

Unlabelled: Rheumatoid arthritis (RA) involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration could be portrayed scintigraphically to monitor noninvasively the effects of therapy on the progress of the disease. For this purpose, labeling of purified autologous monocytes with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) at very high specific radioactivity has recently been developed.

Labeling of autologous monocytes with 99mTc-HMPAO at very high specific radioactivity.

Rheumatoid arthritis of joints involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration can be portrayed scintigraphically in order to monitor noninvasive effects of therapy on the progress of the disease. Scintigraphic detection of inflammation by means of technetium 99m-hexamethylpropylene amine oxime (99mTc-HMPAO)-labeled leukocytes provides a classic example.

Mosaic amino acid conservation in 3D-structures of surface protein and polymerase of hepatitis B virus.

Surface protein and polymerase of hepatitis B virus provide a striking example of gene overlap. Inclusion of more coding constraints in the phylogenetic analysis forces the tree toward accepted topology. Three-dimensional protein modeling demonstrates that participation in local protein function underlies the observed mosaic patterns of amino acid conservation and variability.

Independent evolution of overlapping polymerase and surface protein genes of hepatitis B virus.

The genome of hepatitis B virus (HBV) provides a striking example of gene overlapping. In particular, the surface protein gene S is overlapped completely by the polymerase gene P. Evolutionary constraints in overlapping genes have been demonstrated for many viruses, with one of the two overlapping genes being subjected to positive selection (adaptive evolution), while the other one is subjected to purifying selection.

Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function.

Background: Complete genome sequences of the Astroviridae include human, non-human mammalian and avian species. A consensus topology of astroviruses has been derived from nucleotide substitutions in the full-length genomes and from non-synonymous nucleotide substitutions in each of the three ORFs. Analyses of synonymous substitutions displayed a loss of tree structure, suggesting either saturation of the substitution model or a deviant pattern of synonymous substitutions in certain virus species.