In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratorysyndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closelyrelated to anyof the previouslycharacterized coronaviruses.

Rubella remains an important pathogen globally with approximately 100,000 cases of congenital rubella syndrome estimated to occur each year. Rubella vaccine is highly effective and safe when used across a population and, as a result, endemic rubella transmission has been interrupted in the Americas since 2009. Incomplete rubella vaccination programs result in continued disease transmission as evidenced by recent large outbreaks in Japan and elsewhere. Herein, we provide current results regarding rubella control, elimination and eradication policies, and a brief review of new laboratory diagnostics. In addition, we provide novel information regarding rubella vaccine immunogenetics and review the emerging evidence of inter-individual variability in humoral and cell-mediated innate and adaptive immune responses to rubella vaccine and their association with HLA alleles, haplotypes, and single nucleotide polymorphisms across the human genome. Finally, we conclude with a call for further research in rubella vaccine immunogenetics and its ability to inform a vaccinomics-level approach to novel vaccine candidate development and the need for a next generation vaccine that is affordable, easy to administer, and does not require a cold chain for optimal immunogenicity.

SUMMARYThe antigenic sites recognized by monoclonal antibodies with neutralizing activity for the Sabin vaccine strains of poliovirus of serotypes 1, 2 and 3 have been studied by the isolation and characterization of mutants resistant to neutralization by antibody. Three distinct sites have been identified which are designated site 1, site 2 and site 3. Site 1 includes a region of 12 amino acids of VP1, from residues 89 to 100, and a corresponding region of VP1 has been identified as an antigenic site for poliovirus 2. This site was strongly immunodominant in type 2 and type 3 but was not detected for poliovirus 1. Site 2 is a complex site including residues 220 to 222 from VP1 (site 2a) with residues including 169 and 170 and others of VP2 (site 2b). Both site 2a and site 2b have been detected in type 1 poliovirus, while as yet only site 2b has been detected in type 3 poliovirus. Site 3 is a complex site including residues 286 to 290 from VP1 (site 3a) with residues including 58 and 59 and others of VP3 (site 3b). Both sites 3a and 3b have been detected in type 3 poliovirus, while as yet only site 3b has been detected in type 1 poliovirus. INTRODUCTIONPoliovirus is a picornavirus of the enterovirus genus occurring in three distinct serotypes. The virion consists of a single strand of messenger-sense RNA enclosed in a capsid made up of 60 copies of each of the four structural proteins VP1, VP2, VP3 and VP4. Nucleotide sequences of the genomic RNA of several strains of poliovirus have been published (Kitamura et al., 1981 ;Toyoda et al., 1984;Cann et al., 1984) and the X-ray crystallographic structure of the Mahoney strain of type 1 poliovirus has been solved to 2.9 A (0-29 nm) resolution .

The crystal structure of the Pl/Mahoney poliovirus empty capsid has been determined at 2.9 A resolution. The empty capsids differ from mature virions in that they lack the viral RNA and have yet to undergo a stabilizing maturation cleavage of VPO to yield the mature capsid proteins VP4 and VP2. The outer surface and the bulk of the protein shell are very similar to those of the mature virion. The major differences between the 2 structures are focused in a network formed by the N-terminal extensions of the capsid proteins on the inner surface of the shell. In the empty capsids, the entire N-terminal extension of V P l , as well as portions corresponding to VP4 and the N-terminal extension of VP2, are disordered, and many stabilizing interactions that are present in the mature virion are missing. In the empty capsid, the VPO scissile bond is located some 20 A away from the positions in the mature virion of the termini generated by VPO cleavage. The scissile bond is located on the rim of a trefoilshaped depression in the inner surface of the shell that is highly reminiscent of an RNA binding site in bean pod mottle virus. The structure suggests plausible (and ultimately testable) models for the initiation of encapsidation, for the RNA-dependent autocatalytic cleavage of VPO, and for the role of the cleavage in establishing the ordered N-terminal network and in generating stable virions.Keywords: capsid proteins; empty capsid; encapsidation initiation; maturation cleavage; poliovirus; viral RNA; virion stability Poliovirus is a member of the picornavirus family. This family includes a large number of related small spherical viruses consisting entirely of a protein shell (approximately 300 A in diameter) and a single-stranded RNA genome (-7,500 nucleotides) of positive polarity. The family is subdivided into several genera, including the enteroviruses (polioviruses, coxsackieviruses,

We have investigated the diversity of a hypervariable segment of the human papillomavirus type 16 (HPV-16) genome among 301 virus isolates that were collected from 25 different ethnic groups and geographic locations. Altogether, we distinguished 48 different variants that had diversified from one another along five phylogenetic branches. Variants from two of these branches were nearly completely confined to Africa. Variants from a third branch were the only variants identified in Europeans but occurred at lower frequency in all other ethnic groups. A fourth branch was specific for Japanese and Chinese isolates. A small fraction of all isolates from Asia and from indigenous as well as immigrant populations in the Americas formed a fifth branch. Important patterns of HPV-16 phylogeny suggested coevolution of the virus with people of the three major human races, namely, Africans, Caucasians, and East Asians. But several minor patterns are indicative of smaller bottlenecks of viral evolution and spread, which may correlate with the migration of ethnic groups in prehistoric times. The colonization of the Americas by Europeans and Africans is reflected in the composition of their HPV-16 variants. We discuss arguments that today's HPV-16 genomes represent a degree of diversity that evolved over a large time span, probably exceeding 200,000 years, from a precursor genome that may have originated in Africa. The identification of molecular variants is a powerful epidemiological and phylogenetic tool for revealing the ancient spread of papillomaviruses, whose trace through the world has not yet been completely lost.

Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10−3 subs/site/year and 8.9 x 10−4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.

No abstract

No abstract