Streptococcus mutans is the leading cause of dental caries (tooth decay) worldwide and is considered to be the most cariogenic of all of the oral streptococci. The genome of S. mutans UA159, a serotype c strain, has been completely sequenced and is composed of 2,030,936 base pairs. It contains 1,963 ORFs, 63% of which have been assigned putative functions. The genome analysis provides further insight into how S. mutans has adapted to surviving the oral environment through resource acquisition, defense against host factors, and use of gene products that maintain its niche against microbial competitors. S. mutans metabolizes a wide variety of carbohydrates via nonoxidative pathways, and all of these pathways have been identified, along with the associated transport systems whose genes account for almost 15% of the genome. Virulence genes associated with extracellular adherent glucan production, adhesins, acid tolerance, proteases, and putative hemolysins have been identified. Strain UA159 is naturally competent and contains all of the genes essential for competence and quorum sensing. Mobile genetic elements in the form of IS elements and transposons are prominent in the genome and include a previously uncharacterized conjugative transposon and a composite transposon containing genes for the synthesis of antibiotics of the gramicidin͞bacitracin family; however, no bacteriophage genomes are present.

The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately onethird of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulenceassociated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial ''molecular mimicry'' of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential.

Genomic sequences and expressed sequence tag data for a diverse group of fungi (Saccharomyces cerevisiae, Schizosaccharomyces pombe, Aspergillus nidulans, Neurospora crassa, and Cryptococcus neoformans) provided the opportunity to accurately characterize conserved intronic elements. An examination of large intron data sets revealed that fungal introns in general are short, that 98% or more of them belong to the canonical splice site (ss) class (5GU. . .AG3), and that they have polypyrimidine tracts predominantly in the region between the 5 ss and the branch point. Information content is high in the 5 ss, branch site, and 3 ss regions of the introns but low in the exon regions adjacent to the introns in the fungi examined. The two yeasts have broader intron length ranges and correspondingly higher intron information content than the other fungi. Generally, as intron length increases in the fungi, so does intron information content. Homologs of U2AF spliceosomal proteins were found in all species except for S. cerevisiae, suggesting a nonconventional role for U2AF in the absence of canonical polypyrimidine tracts in the majority of introns. Our observations imply that splicing in fungi may be different from that in vertebrates and may require additional proteins that interact with polypyrimidine tracts upstream of the branch point. Theoretical protein homologs for Nam8p and TIA-1, two proteins that require U-rich regions upstream of the branch point to function, were found. There appear to be sufficient differences between S. cerevisiae and S. pombe introns and the introns of two filamentous members of the Ascomycota and one member of the Basidiomycota to warrant the development of new model organisms for studying the splicing mechanisms of fungi.Based on studies with a limited number of organisms, fungal genes appear to differ from those of higher eukaryotes in that fungal genes have relatively long exons and short introns (14,37,53). From these data, we hypothesized that fungi as a group would have exon and intron features that are similar as well as different from those of higher eukaryotes. Our approach to testing this hypothesis was to compare the exon and intron characteristics of two well-studied members of the Ascomycota group of fungal organisms, the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe (7,12,20,30,34,68), with the intron and exon characteristics of three additional fungi for which genomic sequences and expressed sequence tag (EST) data are available: two filamentous members of the Ascomycota, Aspergillus nidulans and Neurospora crassa (http://www.broad.mit.edu/annotation/fungi /aspergillus/, http://www.broad.mit.edu/annotation/fungi /neurospora/, and http://www.genome.ou.edu/fungal.html) (19,36,72), and a member of the Basidiomycota, Cryptococcus neoformans (http://www-sequence.stanford.edu/group /C.neoformans/ and http://www.genome.ou.edu/cneo.html). The availability of genomic sequences and EST data for the latter three fungi permitted the establishment...

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Varicella-zoster virus (VZV) infection of differentiated cells within the host and establishment of latency likely requires evasion of innate immunity and limits secretion of antiviral cytokines. Here we report that its immediate-early protein ORF61 antagonizes the beta interferon (IFN-␤) pathway. VZV infection down-mod-Varicella-zoster virus (VZV) is ubiquitous in most of the population worldwide and is an alphaherpesvirus restricted to humans. Primary VZV infection begins with inoculation of the respiratory mucosa, followed by cell-associated viremia and the rash of chickenpox. During primary infection, the virus establishes latency in sensory ganglia and can subsequently reactivate to cause shingles (herpes zoster) (3). The VZV genome contains one copy of linear double-strand DNA approximately 125 kb in length and encodes about 70 unique proteins. Similar to other alphaherpesviruses, the expression of VZV genes is assorted temporally into three categories-immediate-early (IE), early (E), and late (L)-and the IE proteins usually play critical roles during VZV life cycles (29).ORF61 encodes a 62-to 66-kDa phosphoprotein (45), which is highly homologous to herpes simplex virus 1 (HSV-1) ICP0 in the RING finger domain and can partially complement the function of ICP0 in ICP0-null HSV-1 (28). Both proteins exhibit regulatory functions, but the difference between them is that ORF61 has either a transactivated or repressive function (16, 31), while ICP0 mostly shows transcriptional activation (12,14). Although ICP0 can inhibit the innate immunity pathway at many levels, such as IRF3 and PML (13,26), little is known about the function of ORF61 in interrupting the innate immunity.The innate immune system is an ancient and nonspecific system that provides the first line of defense against infection. One of the most effective innate antiviral responses is the production of alpha/beta interferon (IFN-␣/␤) and the subsequent induction of interferon-stimulated genes (ISGs) (38). Previous studies have demonstrated that VZV infection stimulates innate immune responses mainly by the production of IFN-␣ and IFN-␥ (1, 2, 27), while IFN-␤ is not detected in serum of VZV-infected patients. This might be explained by the evidence provided by one group that the production of IFN-␤ may be blocked by ORF62 during VZV infection (40).Increasing evidence has shown that ICP0 possesses various antagonistic functions against the host innate immune system