Analogs of LDL Receptor Ligand Motifs in Dengue Envelope and Capsid Proteins as Potential Codes for Cell Entry

It is established that cell entry of low density lipoprotein particles (LLPs) containing Apo B100 and Apo E is mediated by receptors and GAGs. Receptor ligand motifs, XBBBXXBX, XBBXBX, and ΨBΨXB, and mono- and bipartite NLS sequences are abundant in Apo E and Apo B100 as well as in envelope and capsid proteins of dengue viruses 1–4 (DENV1–4). Synthetic, fluorescence-labeled peptides of sequences in DENV2 envelope protein, and DENV3 capsid that include these motifs were used to conduct a qualitative assessment of cell binding and entry capacity using HeLa cells. DENV2 envelope peptide, Dsp2EP, 0564Gly-Gly0595, was shown to bind and remain at the cell surface. In contrast, DENV3 capsid protein peptide, Dsp3CP, 0002Asn-Gln0028, readily enters HeLa cells and accumulates at discrete loci in the nucleus. FITC-labeled dengue synthetic peptides colocalize with low density lipoprotein-CM-DiI and Apo E-CM-DiI to a degree suggesting that dengue viruses may utilize cell entry pathways used by LLPs.

Hepatitis B Virus Seroprevalence and Serology Patterns in a Cohort of HIV Positive Individuals from Harare, Zimbabwe

Zimbabwe is highly endemic for hepatitis B virus (HBV) and also has high human immunodeficiency virus (HIV) prevalence rates which may result in HIV/HBV coinfection, and as HIV/HBV coinfection may affect the classical HBV serology patterns and cause interpretation challenges, we assessed the seroprevalence of HBV in HIV positive patients and determined their serology profiles. This was a cross-sectional study on 957 HIV positive specimens from treatment naive patients. HBV serology tests were done using enzyme immunoassays for the detection of HBV markers in human serum or plasma. Hepatitis B surface antigen (HBsAg) prevalence was 17.1% (males 19.0%, females 15.8%). Previous and/or current HBV exposure was evident in 59.8% of the patients and hepatitis B e antigen markers were present in 103 (10.8%) specimens. There was high prevalence of unusual HBV patterns with 14.1% of total specimens showing an anti-HBc alone profile and an additional 4.3% HBsAg positive specimens that were anti-HBc negative.

Bacteriophages and Their Derivatives as Biotherapeutic Agents in Disease Prevention and Treatment

The application of bacteriophages for the elimination of pathogenic bacteria has received significantly increased attention world-wide in the past decade. This is borne out by the increasing prevalence of bacteriophage-specific conferences highlighting significant and diverse advances in the exploitation of bacteriophages. While bacteriophage therapy has been associated with the Former Soviet Union historically, since the 1990s, it has been widely and enthusiastically adopted as a research topic in Western countries. This has been justified by the increasing prevalence of antibiotic resistance in many prominent human pathogenic bacteria. Discussion of the therapeutic aspects of bacteriophages in this review will include the uses of whole phages as antibacterials and will also describe studies on the applications of purified phage-derived peptidoglycan hydrolases, which do not have the constraint of limited bacterial host-range often observed with whole phages.

Evolution of New Variants/Mutants of JE Virus, Its Effect on Neurovirulence, Antigenicity, Host Immune Responses and Disease Transmission in Endemic Areas

This paper highlights various reasons of evolution of new mutants/variants of JE virus and its effects on neurovirulence, antigenicity, host immune responses, and disease transmission in endemic areas. Virus is reorganizing its genome by making sequence alterations, single site mutations, cluster specific reversions, and amino acid substitutions in neutralizing antigenic sites mainly in N′ glycosylation sites and epitopic regions of S and E proteins. Virus is regularly changing gene order, gene density by making substitution point mutations in important structural genes which make virus envelope proteins. Further, JE virus acquiring new genetic variations and adaptabilities through genetic recombination of wild strains with vaccine strains and assimilating new lethal genes that lead to emergence of molecular variants/mutants. These newly emerged JE virus genotypes have attained the ability to escape the immune defense and show wider resistance against vaccines and therapeutic agents. Thus new strains did significant elevation in the level of neurovirulence, antigenicity and pathogenesis. It is causing very high mortalities in various infant groups and imposing lifelong irreversible disorders in survivors and showing a regular trend of emergence and reemergence in endemic areas. The present review article emphasizes methods to suppress virus replication, reversion of neurovirulence, attenuation and an utmost need of more potential vaccines against cross reactive heterologous genotypes of JE virus to control disease transmission and mortalities occurring in endemic areas.

Natural Selection Determines Synonymous Codon Usage Patterns of Neuraminidase (NA) Gene of the Different Subtypes of Influenza A Virus in Canada

Synonymous codon usage patterns of neuraminidase (NA) gene of 64 subtypes (one is a mixed subtype) of influenza A virus found in Canada were analyzed. In total, 1422 NA sequences were analyzed. Among the subtypes, H1N1 is the prevailing one with 516 NCBI accession records, followed by H3N2, H3N8, and H4N6. The year of 2009 has the highest report records for the NA sequences in Canada, corresponding to the 2009 pandemic event. Correspondence analysis on the RSCU values of the four major subtypes showed that they had distinct clustering patterns in the two-dimensional scatter plot, indicating that different subtypes of IAV utilized different preferential codons. This subtype clustering pattern implied the important influence of natural selection, which could be further evidenced by an extremely flattened regression line in the neutrality plot (GC12 versus G3s plot) and a significant phylogenetic signal on the distribution of different subtypes in the clades of the phylogenetic tree (λ statistic). In conclusion, different subtypes of IAV showed an evolutionary differentiation on choosing different optimal codons. Natural selection played a deterministic role to structure IAV codon usage patterns in Canada.

Recognition of Errors in the Refinement and Validation of Three-Dimensional Structures of AC1 Proteins of Begomovirus Strains by Using ProSA-Web

The structural model of begomovirus AC1 protein is useful for understanding biological function at molecular level and docking study. For this study we have used the ProSA program (Protein Structure Analysis) tool to establish the structure prediction and modeling of protein. This tool was used for refinement and validation of experimental protein structures. Potential problems of protein structures based on energy plots are easily seen by ProSA and are displayed in a three-dimensional manner. In the present study we have selected different AC1 proteins of begomovirus strains (YP_003288785, YP_002004579, and YP_003288773) for structural analysis and display of energy plots that highlight potential problems spotted in protein structures. The 3D models of Rep proteins with recognized errors can be effectively used for in silico docking study for development of potential ligand molecules against begomovirus infection.