The myelin transcription factor 1 (Myt1) gene family is comprised of three zinc finger genes [Myt1, and NZF3] of the structurally unique CCHHC class that are expressed predominantly in the developing CNS. To understand the mechanism by which this family regulates neural differentiation, we searched for interaction partners. In both yeast and a mammalian twohybrid system, Myt1 and Myt1L interacted with Sin3B, a protein that mediates transcriptional repression by binding to histone deacetylases (HDACs). Myt1-Sin3B complexes were coimmunoprecipitated from transfected mammalian cells and included HDAC1 and HDAC2. Myt1 and Myt1L could partner with all three Sin3B isoforms, the long form (Sin3B LF ) that includes the HDAC-binding domain, and the two short forms (Sin3B SF293 and Sin3B SF302 ) that lack this domain and may consequently antagonize Sin3B LF /HDAC-mediated co-repression. Myt1 or Myt1L interactions with the HDAC-binding form of Sin3B conferred repression on a heterologous promoter. Oligodendrocytes were shown to express transcripts encoding each of the Sin3B isoforms. We present a model in which the Myt1 family of zinc finger proteins, when bound to a neural promoter, can recruit Sin3B. Depending on the relative availability of Sin3B isoforms, the Myt1 gene family may favor the silencing of genes during neural development.Keywords histone deacetylase; mSin3; Myt1; repression; transcription; zinc finger Abbreviations usedCMV, cytomegalovirus; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HDAC, histone deacetylase; Myt1, myelin transcription factor 1; Myt1L, myelin transcription factor 1 like; NZF, neural zinc finger; PAH, paired amphipathic helicalThe specification and differentiation of neural cells is orchestrated at the transcriptional level by two classes of factors, those with chromatin-remodeling activities that regulate how tightly histones wrap up DNA in nucleosomal structures, and those that directly contact target genes and/or other transcription factors and ultimately determine whether the basal machinery initiates transcription. These two classes are functionally and physically linked, as co-activator complexes have an associated histone acetylase whose activity relaxes chromatin structure to promote accessibility of DNA-binding proteins, and co-repressor complexes have an opposing histone deacetylase (HDAC) activity (Wolffe et al. 2000). Key to this linkage are sequencespecific transcription factors that can recruit HDACs or acetylases. The zinc finger protein RE1-silencing transcription factor is one such factor that represses many neuron-specific genes through multiple HDAC complexes (Grimes et al. 2000;Ballas et al. 2001).The myelin transcription factor 1 (Myt1) family represents neural zinc finger proteins of a structurally novel CCHHC class that were originally cloned by their binding to the promoter of the most abundantly expressed myelin gene, proteolipid protein (Kim and Hudson 1992). The consensus DNA-binding domain of the Myt1 family is Cys-X 4 -Cys-X 4 -His-X 7 -His-X 5 -Cy...

Summary. The S and M segments of a hantavirus, enzymatically amplified from tissues of Cloudland deer mice (Peromyscus maniculatus nubiterrae) captured during 1985 in West Virginia, diverged from strains of Four Corners virus from the southwestern United States bymore than 16% and 6% at the nucleotide and amino acid levels, respectively. Phylogenetic analysis suggested that this virus strain (designated Monongahela) forms a possible evolutionary link between the Four Corners and New York hantaviruses.

Serological screening for human T-lymphotropic virus type 1 (HTLV-1) parallels the standard screening process for human immunodeficiency virus (HIV), in which samples found positive by enzyme-linked immunosorbent assay (ELISA) are confirmed with a modified Western blot procedure. There are a significant number of cases in which HTLV-1/2 ELISA-positive specimens demonstrate an incomplete banding pattern on this Western blot. Individuals providing these atypical antibody responses are categorized as seroindeterminate for HTLV-1/2. Although HTLV-1 genomic sequences are readily detectable in the peripheral blood lymphocytes (PBL) of seropositive individuals, previous studies have repeatedly demonstrated that PBL from the vast majority of HTLV-1/2 seroindeterminate individuals are PCR negative for HTLV-1. As a result, identification of the agent responsible for this indeterminate reactivity has been of interest. We have generated an HTLV-1-positive B-cell line (SI-1 B) from one of these seroindeterminate individuals. Previous screening for HTLV-1 in PBL from this patient had been routinely negative by primary PCR; however, HTLV-1 tax had been periodically detected by nested PCR. DNA sequence data generated with genomic DNA from the SI-1 B cell line and HTLV-1-specific primers demonstrated the presence of a full-length viral genome with >97% homology to the Cosmopolitan form of HTLV-1. A 12-bp deletion was identified in the 3-gag/5-prot region, which would predict translation of altered or nonfunctional proteins from these genes. We propose that this HTLV-1/2-seroindeterminate patient is infected with a prototypic form of HTLV-1 at an extremely low viral load and that this finding may explain HTLV-1/2 seroindeterminate reactivity in at least a subset of these individuals.

Nested primer-based polymerase chain reaction was employed to determine the frequency of latent infection with human herpesvirus 6 (HHV-6) among healthy adults from Bratislava, Slovak Republic. A 592-bp region, upstream from the gene encoding the putative large tegument protein of HHV-6, was amplified from DNA extracted from peripheral blood mononuclear cells (PBMC) of only one of 29 seropositive adults, suggesting that as few as 1 in 10(5) PBMC may be infected with the virus. Direct sequencing of the 592-bp fragment indicated that the virus harbored by the seropositive Slovak subject (designated B38) differed by only 3 nucleotides from an HHV-6 variant B strain (R-147) isolated from an American infant with a roseola-like illness and by 32 bases from the variant A strain GS isolated from a patient with lymphadenopathy (5.4% sequence divergence). None of these strains had a deoxyadenosine at base position 1251, when compared to the published sequence of strain GS clone pZVH14. Although this discrepancy did not affect the large tegument protein gene, it altered the predicted amino acid sequences of two putative proteins coded by open-reading frames 1 and 2 (ORF 1 and ORF 2) located upstream from this gene.