Search

For an infinite family of monogenic trinomials $P(X) = X^3\pm 3rbX-b$ in $\mathbb{Z}\lbrack X\rbrack$, arithmetical invariants of the cubic number field $L = \mathbb{Q}(\theta)$, generated by a zero $\theta$ of $P(X)$, and of its Galois closure $N = L(\sqrt{d(L)})$ are determined. The conductor $f$ of the cyclic cubic relative extension $N/K$, where $K = \mathbb{Q}(\sqrt{d(L)})$ denotes the unique quadratic subfield of $N$, is proved to be of the form $3^eb$ with $e\in\lbrace 1,2\rbrace$, which admits statements concerning primitive ambiguous principal ideals, lattice minima, and independent units in $L$. The number $m$ of non-isomorphic cubic fields $L_1,\ldots,L_m$ sharing a common discriminant $d(L_i) = d(L)$ with $L$ is determined., Comment: 25 pages, 14 tables

For finite metabelian 3-groups M with elementary bicyclic commutator quotient M/M' = C3*C3, coclass cc(M) in {4,6}, and transfer kernel type F, the smallest Schur sigma-groups S with second derived quotient S/S" = M are determined. Evidence is provided of arithmetical realizations of these groups by second 3-class groups M = Gal(F(3,2,K)/K), respectively 3-class field tower groups S = Gal(F(3,infty,K)/K), of imaginary quadratic number fields K=Q(sqrt{d})., Comment: 17 pages, 15 tables

Let $p\equiv 1\,(\mathrm{mod}\,9)$ be a prime number and $\zeta_3$ be a primitive cube root of unity. Then $\mathrm{k}=\mathbb{Q}(\sqrt[3]{p},\zeta_3)$ is a pure metacyclic field with group $\mathrm{Gal}(\mathrm{k}/\mathbb{Q})\simeq S_3$. In the case that $\mathrm{k}$ possesses a $3$-class group $C_{\mathrm{k},3}$ of type $(9,3)$, the capitulation of $3$-ideal classes of $\mathrm{k}$ in its unramified cyclic cubic extensions is determined, and conclusions concerning the maximal unramified pro-$3$-extension $\mathrm{k}_3^{(\infty)}$ of $\mathrm{k}$ are drawn., Comment: 23 pages, 7 Figures, 1 Table

Let zeta5 be a primitive fifth root of unity and d<>1 be a quadratic fundamental discriminant not divisible by 5. For the 5-dual cyclic quartic field M=Q((zeta5-zeta5^-1)*d^1/2) of the quadratic fields k1=Q(d^1/2) and k2=Q((5*d)^1/2) in the sense of the quintic reflection theorem, the possibilities for the isomophism type of the Galois group G(5,2)M=Gal(M(5,2)/M) of the second Hilbert 5-class field M(5,2) of M are investigated, when the 5-class group Cl5(M) is elementary bicyclic of rank two. Usually, the maximal unramified pro-5-extension M(5,infinity) of M coincides with M(5,2) already. The precise length ell5(M) of the 5-class tower of M is determined, when G(5,2)M is of order less than or equal to 5^5. Theoretical results are underpinned by the actual computation of all 83, respectively 93, cases in the range 0, Comment: 25 pages, 4 figures, 8 tables

Barrucand and Cohn's theory of principal factorizations in pure cubic fields \(\mathbb{Q}(\sqrt[3]{D})\) and their Galois closures \(\mathbb{Q}(\zeta_3,\sqrt[3]{D})\) with \(3\) types is generalized to pure quintic fields \(L=\mathbb{Q}(\sqrt[5]{D})\) and pure metacyclic fields \(N=\mathbb{Q}(\zeta_5,\sqrt[5]{D})\) with \(13\) possible types. The classification is based on the Galois cohomology of the unit group \(U_N\), viewed as a module over the automorphism group \(\mathrm{Gal}(N/K)\) of \(N\) over the cyclotomic field \(K=\mathbb{Q}(\zeta_5)\), by making use of theorems by Hasse and Iwasawa on the Herbrand quotient of the unit norm index \((U_K:N_{N/K}(U_N))\) by the number \(\#(\mathcal{P}_{N/K}/\mathcal{P}_K)\) of primitive ambiguous principal ideals, which can be interpreted as principal factors of the different \(\mathfrak{D}_{N/K}\). The precise structure of the group of differential principal factors is determined with the aid of kernels of norm homomorphisms and central orthogonal idempotents. A connection with integral representation theory is established via class number relations by Parry and Walter involving the index of subfield units \((U_N:U_0)\). Generalizing criteria for the Polya property of Galois closures \(\mathbb{Q}(\zeta_3,\sqrt[3]{D})\) of pure cubic fields \(\mathbb{Q}(\sqrt[3]{D})\) by Leriche and Zantema, we prove that pure metacyclic fields \(N=\mathbb{Q}(\zeta_5,\sqrt[5]{D})\) of only \(1\) type cannot be Polya fields. All theoretical results are underpinned by extensive numerical verifications of the \(13\) possible types and their statistical distribution in the range \(2\le D, Comment: 30 pages, 10 sections, 6 tables

Let [Formula: see text] denote the discriminant of a real quadratic field. For all bicyclic biquadratic fields [Formula: see text], having a [Formula: see text]-class group of type [Formula: see text], the possibilities for the isomorphism type of the Galois group [Formula: see text] of the second Hilbert [Formula: see text]-class field [Formula: see text] of [Formula: see text] are determined. For each coclass graph [Formula: see text], [Formula: see text], in the sense of Eick, Leedham-Green, Newman and O’Brien, the roots [Formula: see text] of even branches of exactly one coclass tree and, in the case of even coclass [Formula: see text], additionally their siblings of depth [Formula: see text] and defect [Formula: see text], turn out to be admissible. The principalization type [Formula: see text] of [Formula: see text]-classes of [Formula: see text] in its four unramified cyclic cubic extensions [Formula: see text] is given by [Formula: see text] for [Formula: see text], and by [Formula: see text] for [Formula: see text]. The theory is underpinned by an extensive numerical verification for all [Formula: see text] fields [Formula: see text] with values of [Formula: see text] in the range [Formula: see text], which supports the assumption that all admissible vertices [Formula: see text] will actually be realized as Galois groups [Formula: see text] for certain fields [Formula: see text], asymptotically.

Let $k=k_0(\sqrt[3]{d})$ be a cubic Kummer extension of $k_0=\mathbb{Q}(\zeta_3)$ with $d>1$ a cube-free integer and $\zeta_3$ a primitive third root of unity. Denote by $C_{k,3}^{(\sigma)}$ the $3$-group of ambiguous classes of the extension $k/k_0$ with relative group $G=\operatorname{Gal}(k/k_0)=\langle\sigma\rangle$. The aims of this paper are to characterize all extensions $k/k_0$ with cyclic $3$-group of ambiguous classes $C_{k,3}^{(\sigma)}$ of order $3$, to investigate the multiplicity $m(f)$ of the conductors $f$ of these abelian extensions $k/k_0$, and to classify the fields $k$ according to the cohomology of their unit groups $E_{k}$ as Galois modules over $G$. The techniques employed for reaching these goals are relative $3$-genus fields, Hilbert norm residue symbols, quadratic $3$-ring class groups modulo $f$, the Herbrand quotient of $E_{k}$, and central orthogonal idempotents. All theoretical achievements are underpinned by extensive computational results., Comment: 24 pages, 7 tables, 3 figures

The aim of this chapter is to provide an adequate graph theoretic framework for the description of periodic bifurcations which have recently been discovered in descendant trees of finite p-groups. The graph theoretic concepts of rooted in-trees with weighted vertices and edges perfectly admit an abstract formulation of the group theoretic notions of successive extensions, nuclear rank, multifurcation, and step size. Since all graphs in this chapter are infinite and dense, we use methods of pattern recognition and independent component analysis to reduce the complex structure to periodically repeating finite patterns. The method of group cohomology yields subgraph isomorphisms required for proving the periodicity of branches along mainlines. Finally the mainlines are glued together with the aid of infinite limit groups whose finite quotients form the vertices of mainlines. The skeleton of the infinite graph is a countable union of infinite mainlines, connected by periodic bifurcations. Each mainline is the backbone of a minimal subtree consisting of a periodically repeating finite pattern of branches with bounded depth. A second periodicity is caused by isomorphisms between all minimal subtrees which make up the complete infinite graph. Only the members of the first minimal tree are metabelian and the bifurcations, which were unknown up to now, open the long desired door to non-metabelian extensions whose second derived quotients are isomorphic to the metabelian groups. An application of this key result to algebraic number theory solves the problem of p-class field towers of exact length three.

The p-group generation algorithm is used to verify that the Hilbert 3-class field tower has length 3 for certain imaginary quadratic fields K with 3-class group Cl 3 ( K ) ≅ [ 3 , 3 ] . Our results provide the first examples of finite p-class towers of length >2 for an odd prime p.

For a prime \(p\ge 2\) and a number field K with p-class group of type (p,p) it is shown that the class, coclass, and further invariants of the metabelian Galois group \(G=Gal(F_p^2(K) | K)\) of the second Hilbert p-class field \(F_p^2(K)\) of K are determined by the p-class numbers of the unramified cyclic extensions \(N_i | K\), \(1\le i\le p+1\), of relative degree p. In the case of a quadratic field \(K=\mathbb{Q}(\sqrt{D})\) and an odd prime \(p\ge 3\), the invariants of G are derived from the p-class numbers of the non-Galois subfields \(L_i | \mathbb{Q}\) of absolute degree p of the dihedral fields \(N_i\). As an application, the structure of the automorphism group \(G=Gal(F_3^2(K) | K)\) of the second Hilbert 3-class field \(F_3^2(K)\) is analysed for all quadratic fields K with discriminant \(-10^6, Comment: 22 pages, 9 tables

Despite their close phylogenetic relationship, natural intertypic reassortants between influenza A (FluA) and B (FluB) viruses have not been described. Inefficient polymerase assembly of the three polymerase subunits may contribute to this incompatibility, especially because the known protein-protein interaction domains, including the PA-binding domain of PB1, are highly conserved for each virus type. Here we show that substitution of the FluA PA-binding domain (PB1-A(1-25)) with that of FluB (PB1-B(1-25)) is accompanied by reduced polymerase activity and viral growth of FluA. Consistent with these findings, surface plasmon resonance spectroscopy measurements revealed that PA of FluA exhibits impaired affinity to biotinylated PB1-B(1-25) peptides. PA of FluB showed no detectable affinity to biotinylated PB1-A(1-25) peptides. Consequently, FluB PB1 harboring the PA-binding domain of FluA (PB1-AB) failed to assemble with PA and PB2 into an active polymerase complex. To regain functionality, we used a single amino acid substitution (T6Y) known to confer binding to PA of both virus types, which restored polymerase complex formation but surprisingly not polymerase activity for FluB. Taken together, our results demonstrate that the conserved virus type-specific PA-binding domains differ in their affinity to PA and thus might contribute to intertypic exclusion of reassortants between FluA and FluB viruses.

The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1–2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses.

The assembly of the polymerase complex of influenza A virus from the three viral polymerase subunits PB1, PB2, and PA is required for viral RNA synthesis. We show that peptides which specifically bind to the protein-protein interaction domains in the subunits responsible for complex formation interfere with polymerase complex assembly and inhibit viral replication. Specifically, we provide evidence that a 25-amino-acid peptide corresponding to the PA-binding domain of PB1 blocks the polymerase activity of influenza A virus and inhibits viral spread. Targeting polymerase subunit interactions therefore provides a novel strategy to develop antiviral compounds against influenza A virus or other viruses.

The phosphoprotein P of Borna disease virus (BDV) is an essential cofactor of the viral RNA-dependent RNA polymerase. It is preferentially phosphorylated at serine residues 26 and 28 by protein kinase C ε (PKCε) and, to a lesser extent, at serine residues 70 and 86 by casein kinase II (CKII). To determine whether P phosphorylation is required for viral polymerase activity, we generated P mutants lacking either the PKCε or the CKII phosphate acceptor sites by replacing the corresponding serine residues with alanine (A). Alternatively, these sites were replaced by aspartic acid (D) to mimic phosphorylation. Functional characterization of the various mutants in the BDV minireplicon assay revealed that D substitutions at the CKII sites inhibited the polymerase-supporting activity of P, while A substitutions maintained wild-type activity. Likewise, D substitutions at the PKC sites did not impair the cofactor function of BDV-P, whereas A substitutions at these sites led to increased activity. Interestingly, recombinant viruses could be rescued only when P mutants with modified PKCε sites were used but not when both CKII sites were altered. PKCε mutant viruses showed a reduced capacity to spread in cell culture, while viral RNA and protein expression levels in persistently infected cells were almost normal. Further mutational analyses revealed that substitutions at individual CKII sites were, with the exception of a substitution of A for S86, detrimental for viral rescue. These data demonstrate that, in contrast to other viral P proteins, the cofactor activity of BDV-P is negatively regulated by phosphorylation.

The p-class tower $F_p^\infty(k)$ of a number field k is its maximal unramified pro-p extension. It is considered to be known when the p-tower group, that is the Galois group $G:=Gal(F_p^\infty(k)/k)$, can be identified by an explicit presentation. The main intention of this article is to characterize assigned finite 3-groups uniquely by abelian quotient invariants of subgroups of finite index, and to provide evidence of actual realizations of these groups by 3-tower groups G of real quadratic fields $K=Q(\sqrt{d})$ with 3-capitulation type (0122) or (2034)., 25 pages, 5 figures; presented at the 22nd Czech and Slovak International Conference on Number Theory in Liptovsky Jan, Slovakia, on August 31, 2015

Cellular factors that associate with the influenza A viral ribonucleoprotein (vRNP) are presumed to play important roles in the viral life cycle. To date, interaction screens using individual vRNP components, such as the nucleoprotein or viral polymerase subunits, have revealed few cellular interaction partners. To improve this situation, we performed comprehensive, proteomics-based screens to identify cellular factors associated with the native vRNP and viral polymerase complexes. Reconstituted vRNPs were purified from human cells using Strep-tagged viral nucleoprotein (NP-Strep) as bait, and co-purified cellular factors were identified by mass spectrometry (MS). In parallel, reconstituted native influenza A polymerase complexes were isolated using tandem affinity purification (TAP)-tagged polymerase subunits as bait, and co-purified cellular factors were again identified by MS. Using these techniques, we identified 41 proteins that co-purified with NP-Strep-enriched vRNPs and four cellular proteins that co-purified with the viral polymerase complex. Two of the polymerase-associated factors, importin-beta3 and PARP-1, represent novel interaction partners. Most cellular proteins previously shown to interact with either viral NP and/or vRNP were also identified using our method, demonstrating its sensitivity. Co-immunoprecipitation studies in virus-infected cells using selected novel interaction partners, including nucleophosmin (NPM), confirmed their association with vRNP. Immunofluorescence analysis further revealed that NPM is recruited to sites of viral transcription and replication in infected cells. Additionally, overexpression of NPM resulted in increased viral polymerase activity, indicating its role in viral RNA synthesis. In summary, the proteomics-based approaches used in this study represent powerful tools to identify novel vRNP-associated cellular factors for further characterization.

Explicit expressions for the transfers \(V_i\) from a metabelian p-group G of coclass cc(G)=1 to its maximal normal subgroups \(M_i\) \((1\le i\le p+1)\) are derived by means of relations for generators. The expressions for the exceptional case p=2 differ significantly from the standard case of odd primes \(p\ge 3\). In both cases the transfer kernels \(Ker(V_i)\) are calculated and the principalisation type of the metabelian p-group is determined, if G is realised as the Galois group \(Gal(F_p^2(K) | K)\) of the second Hilbert p-class field \(F_p^2(K)\) of an algebraic number field K. For certain metabelian 3-groups G with abelianisation \(G/G^{\prime}\) of type (3,3) and of coclass \(cc(G)=r\ge 3\), it is shown that the principalisation type determines the position of G on the coclass graph G(3,r) in the sense of Eick and Leedham-Green., 22 pages, 7 tables

Let p denote an odd prime. For all p-admissible conductors c over a quadratic number field \(K=\mathbb{Q}(\sqrt{d})\), p-ring spaces \(V_p(c)\) modulo c are introduced by defining a morphism \(\psi:\,f\mapsto V_p(f)\) from the divisor lattice \(\mathbb{N}\) of positive integers to the lattice S of subspaces of the direct product \(V_p\) of the p-elementary class group \(C/C^p\) and unit group \(U/U^p\) of K. Their properties admit an exact count of all extension fields N over K, having the dihedral group of order 2p as absolute Galois group \(Gal(N | \mathbb{Q})\) and sharing a common discriminant \(d_N\) and conductor c over K. The number \(m_p(d,c)\) of these extensions is given by a formula in terms of positions of p-ring spaces in S, whose complexity increases with the dimension of the vector space \(V_p\) over the finite field \(\mathbb{F}_p\), called the modified p-class rank \(\sigma_p\) of K. Up to now, explicit multiplicity formulas for discriminants were known for quadratic fields with \(0\le\sigma_p\le 1\) only. Here, the results are extended to \(\sigma_p=2\), underpinned by concrete numerical examples., Comment: 27 pages, 6 figures, 11 tables, presented at the 122nd Annual DMV Meeting 2012, University of the Saarland, Sarrebruck, FRG, 18 September 2012

General concepts and strategies are developed for identifying the isomorphism type of the second p-class group \(G=Gal(F_p^2(K) | K)\), that is the Galois group of the second Hilbert p-class field \(F_p^2(K)\), of a number field K, for a prime p. The isomorphism type determines the position of G on one of the coclass graphs G(p,r), \(r\ge 0\), in the sense of Eick, Leedham-Green, and Newman. It is shown that, for special types of the base field K and of its p-class group \(Cl_p(K)\), the position of G is restricted to certain admissible branches of coclass trees by selection rules. Deeper insight, in particular, the density of population of individual vertices on coclass graphs, is gained by computing the actual distribution of second p-class groups G for various series of number fields K having p-class groups \(Cl_p(K)\) of fixed type and p in {2,3,5,7}., Comment: 44 pages, 11 figures, presented at the 27th Journ\'ees Arithm\'etiques, Faculty of Mathematics and Informatics, Vilnius University, Vilnius, Lithuania, 1 July 2011

For an algebraic number field K with 3-class group \(Cl_3(K)\) of type (3,3), the structure of the 3-class groups \(Cl_3(N_i)\) of the four unramified cyclic cubic extension fields \(N_i\), \(1\le i\le 4\), of K is calculated with the aid of presentations for the metabelian Galois group \(G_3^2(K)=Gal(F_3^2(K) | K)\) of the second Hilbert 3-class field \(F_3^2(K)\) of K. In the case of a quadratic base field \(K=\mathbb{Q}(\sqrt{D})\) it is shown that the structure of the 3-class groups of the four \(S_3\)-fields \(N_1,\ldots,N_4\) frequently determines the type of principalization of the 3-class group of K in \(N_1,\ldots,N_4\). This provides an alternative to the classical principalization algorithm by Scholz and Taussky. The new algorithm, which is easily automatizable and executes very quickly, is implemented in PARI/GP and is applied to all 4596 quadratic fields K with 3-class group of type (3,3) and discriminant \(-10^6, Comment: 33 pages, 2 figures, presented at the Joint CSASC Conference, Danube University, Krems, Austria, September 2011

Some formulas for multiplicities of pure cubic discriminants are generalized to the case of a pure field of arbitrary odd prime degree.

Virus-infected cells secrete a broad range of interferons (IFN) which confer resistance to yet uninfected cells by triggering the synthesis of antiviral factors. The relative contributions of the various IFN subtypes to innate immunity against virus infections remain elusive. IFN-α, IFN-β, and other type I IFN molecules signal through a common, universally expressed cell surface receptor, whereas type III IFN (IFN-λ) uses a distinct cell-type-specific receptor complex for signaling. Using mice lacking functional receptors for type I IFN, type III IFN, or both, we found that IFN-λ plays an important role in the defense against several human pathogens that infect the respiratory tract, such as influenza A virus, influenza B virus, respiratory syncytial virus, human metapneumovirus, and severe acute respiratory syndrome (SARS) coronavirus. These viruses were more pathogenic and replicated to higher titers in the lungs of mice lacking both IFN receptors than in mice with single IFN receptor defects. In contrast, Lassa fever virus, which infects via the respiratory tract but primarily replicates in the liver, was not influenced by the IFN-λ receptor defect. Careful analysis revealed that expression of functional IFN-λ receptor complexes in the lung and intestinal tract is restricted to epithelial cells and a few other, undefined cell types. Interestingly, we found that SARS coronavirus was present in feces from infected mice lacking receptors for both type I and type III IFN but not in those from mice lacking single receptors, supporting the view that IFN-λ contributes to the control of viral infections in epithelial cells of both respiratory and gastrointestinal tracts.

Gene expression of nonsegmented negative-strand RNA viruses is regulated at the transcriptional level and relies on the canonical 5′-end-dependent translation of capped viral mRNAs. Here, we have used internal ribosome entry sites (IRES) from picornaviruses to control the expression level of the phosphoprotein P of the neurotropic rabies virus (RV; Rhabdoviridae ), which is critically required for both viral replication and escape from the host interferon response. In a dual luciferase reporter RV, the IRES elements of poliovirus (PV) and human rhinovirus type 2 (HRV2) were active in a variety of cell lines from different host species. While a generally lower activity of the HRV2 IRES was apparent compared to the PV IRES, specific deficits of the HRV2 IRES in neuronal cell lines were not observed. Recombinant RVs expressing P exclusively from a bicistronic nucleoprotein (N)-IRES-P mRNA showed IRES-specific reduction of replication in cell culture and in neurons of organotypic brain slice cultures, an increased activation of the beta interferon (IFN-β) promoter, and increased sensitivity to IFN. Intracerebral infection revealed a complete loss of virulence of both PV- and HRV2 IRES-controlled RV for wild-type mice and for transgenic mice lacking a functional IFN-α receptor (IFNAR −/− ). The virulence of HRV2 IRES-controlled RV was most severely attenuated and could be demonstrated only in newborn IFNAR −/− mice. Translational control of individual genes is a promising strategy to attenuate replication and virulence of live nonsegmented negative-strand RNA viruses and vectors and to study the function of IRES elements in detail.

The ML protein of Thogoto virus, a tick-transmitted orthomyxovirus, is a splice variant of the viral matrix protein and antagonizes the induction of antiviral type I interferon (IFN). Here we identified the general RNA polymerase II transcription factor IIB (TFIIB) as an ML-interacting protein. Overexpression of TFIIB neutralized the inhibitory effect of ML on IRF3-mediated promoter activation. Moreover, a recombinant virus expressing a mutant ML protein unable to bind TFIIB was severely impaired in its ability to suppress IFN induction. We concluded that TFIIB binding is required for the IFN antagonist effect exerted by ML. We further demonstrate that the ML-TFIIB interaction has surprisingly little impact on gene expression in general, while a strong negative effect is observed for IRF3- and NF-κB-regulated promoters.

We have recently shown that the matrix protein M of Borna disease virus (BDV) copurifies with the affinity-purified nucleoprotein (N) from BDV-infected cells, suggesting that M is an integral component of the viral ribonucleoprotein complex (RNP). However, further studies were hampered by the lack of appropriate tools. Here we generated an M-specific rabbit polyclonal antiserum to investigate the intracellular distribution of M as well as its colocalization with other viral proteins in BDV-infected cells. Immunofluorescence analysis revealed that M is located both in the cytoplasm and in nuclear punctate structures typical for BDV infection. Colocalization studies indicated an association of M with nucleocapsid proteins in these nuclear punctate structures. In situ hybridization analysis revealed that M also colocalizes with the viral genome, implying that M associates directly with viral RNPs. Biochemical studies demonstrated that M binds specifically to the phosphoprotein P but not to N. Binding of M to P involves the N terminus of P and is independent of the ability of P to oligomerize. Surprisingly, despite P-M complex formation, BDV polymerase activity was not inhibited but rather slightly elevated by M, as revealed in a minireplicon assay. Thus, unlike M proteins of other negative-strand RNA viruses, BDV-M seems to be an integral component of the RNPs without interfering with the viral polymerase activity. We propose that this unique feature of BDV-M is a prerequisite for the establishment of BDV persistence.

The X protein of Borna disease virus (BDV) negatively regulates viral polymerase activity. With a BDV mini-replicon system, 30 % inhibition of polymerase activity was observed at an X to phosphoprotein (P) plasmid ratio of 1 : 6 and 100 % inhibition at a ratio of 1 : 1. It was therefore hypothesized that (i) the X : P ratio in infected cells is not significantly higher than 1 : 6 to prevent complete inhibition of polymerase activity and (ii) X is not efficiently incorporated into viral particles, allowing efficient replication early in infection. To test these assumptions, a monoclonal antibody directed against BDV X was generated. Immunofluorescence analysis revealed co-localization of X with the nucleoprotein (N) and P in the nucleus, as well as in the cytoplasm of BDV-infected cells. Quantification of viral protein levels by Western blot analysis, using purifiedEscherichia coli-derived X, P and N as protein standards, revealed an X : P : N ratio in BDV-infected cells of approximately 1 : 6 : 40. However, only traces of X could be detected in purified BDV stock, suggesting that X is excluded from virus particles. These results indicate that X is a non-structural protein. The lack of X in virus particles may facilitate polymerase activity early in infection; however, the presence of X in persistently infected cells may result in partial inhibition of the polymerase and thus contribute to viral persistence.

The biochemical purification and analysis of viral ribonucleoprotein complexes (RNPs) of negative-strand RNA viruses is hampered by the lack of suitable tags that facilitate specific enrichment of these complexes. We therefore tested whether fusion of the tandem-affinity-purification (TAP) tag to the main component of viral RNPs, the nucleoprotein, might allow the isolation of these RNPs from cells. We constitutively expressed TAP-tagged nucleoprotein of Borna disease virus (BDV) in cells persistently infected with this virus. The TAP-tagged bait was efficiently incorporated into viral RNPs, did not interfere with BDV replication and was also packaged into viral particles. Native purification of the tagged protein complexes from BDV-infected cells by two consecutive affinity columns resulted in the isolation of several viral proteins, which were identified by MS analysis as the matrix protein, the two forms of the nucleoprotein and the phosphoprotein. In addition to the viral proteins, RT-PCR analysis revealed the presence of viral genomic RNA. Introduction of further protease cleavage sites within the TAP-tag significantly increased the purification yield. These results demonstrate that purification of TAP-tagged viral RNPs is possible and efficient, and may therefore provide new avenues for biochemical and functional studies of these complexes.

In the hippocampus of Borna disease virus (BDV)-infected newborn rats, dentate granule cells undergo progressive cell death. BDV is noncytolytic, and the pathogenesis of this neurodevelopmental damage in the absence of immunopathology remains unclear. A suitable model system to study early events of the pathology is lacking. We show here that organotypic hippocampal slice cultures from newborn rat pups are a suitable ex vivo model to examine BDV neuropathogenesis. After challenging hippocampal slice cultures with BDV, we observed a progressive loss of calbindin-positive granule cells 21 to 28 days postinfection. This loss was accompanied by reduced numbers of mossy fiber boutons when compared to mock-infected cultures. Similarly, the density of dentate granule cell axons, the mossy fiber axons, appeared to be substantially reduced. In contrast, hilar mossy cells and pyramidal neurons survived, although BDV was detectable in these cells. Despite infection of dentate granule cells 2 weeks postinfection, the axonal projections of these cells and the synaptic connectivity patterns were comparable to those in mock-infected cultures, suggesting that BDV-induced damage of granule cells is a postmaturation event that starts after mossy fiber synapses are formed. In summary, we find that BDV infection of rat organotypic hippocampal slice cultures results in selective neuronal damage similar to that observed with infected newborn rats and is therefore a suitable model to study BDV-induced pathology in the hippocampus.

Viruses able to infect the central nervous system (CNS) are increasingly being recognized as important factors that can cause mental diseases by interfering with neuronal plasticity. The mechanisms whereby such infections disturb brain functions are beginning to emerge. Borna disease virus (BDV), which causes a persistent infection of neurons without direct cytolysis in several mammalian hosts, has recently gained interest as a unique model to study the mechanisms of viral interference with neuronal plasticity. This review will summarize several hypotheses that have been put forward to explain possible levels of BDV interference with brain function.

We have reported earlier that replacement of the N(pro) gene of classical swine fever virus (CSFV) by the murine ubiquitin gene only slightly affects the characteristics of virus replication in the porcine kidney cell line SK-6 [J. Virol. 72 (1998) 7681]. Here, for the moderately virulent CSFV strain Alfort/187 as well as for the highly virulent strain Eystrup we show that the respective N(pro)-deleted viruses are attenuated. Vaccination of pigs with either of the two deletion mutants resulted in the induction of a strong antibody response. Animals were protected against challenge with a lethal dose of highly virulent CSFV indicating that N(pro) deletion mutants are excellent candidates for a modified live virus vaccine. A chimeric virus obtained by replacement of the N(pro) gene in the Eystrup virus by the corresponding sequence of the avirulent CSFV vaccine strain Riems resulted in a virus that was highly virulent. This indicates that the virulence of CSFV correlates with the presence of N(pro) and also suggests that N(pro) is not responsible for the varying virulence observed between individual strains of CSFV.

The virulence of classical swine fever virus (CSFV) strains including established laboratory strains as well as field isolates ranges from avirulent to highly virulent. Here, we describe the construction and characterisation of two cDNA-derived CSFV strains, each corresponding to one of these extremes. The recombinant virus vEy-37 caused acute disease indistinguishable from that provoked by infection with the highly virulent parent strain Eystrup. In contrast, vRiems-3, a molecular clone of the CSFV vaccine strain Riems, was avirulent and induced protective immunity in pigs. After repeated passage of vEy-37 in porcine kidney SK-6 cells adaptive mutations in the Erns gene were observed. The respective reconstructed mutant virus grew to titres that were almost 4 log units higher when compared to vEy-37. The mutation in the Erns gene had only a minor effect on the virulence of the virus. The complete genomic sequences of the two CSFV strains, Eystrup and Riems, have been deposited in GenBank (accession number AF326963 for CSFV Eystrup, AY259122 for CSFV Riems/IVI).

There is an urgent need for new drugs against influenza type A and B viruses due to incomplete protection by vaccines and the emergence of resistance to current antivirals. The influenza virus polymerase complex, consisting of the PB1, PB2 and PA subunits, represents a promising target for the development of new drugs. We have previously demonstrated the feasibility of targeting the protein-protein interaction domain between the PB1 and PA subunits of the polymerase complex of influenza A virus using a small peptide derived from the PA-binding domain of PB1. However, this influenza A virus-derived peptide did not affect influenza B virus polymerase activity. Here we report that the PA-binding domain of the polymerase subunit PB1 of influenza A and B viruses is highly conserved and that mutual amino acid exchange shows that they cannot be functionally exchanged with each other. Based on phylogenetic analysis and a novel biochemical ELISA-based screening approach, we were able to identify an influenza A-derived peptide with a single influenza B-specific amino acid substitution which efficiently binds to PA of both virus types. This dual-binding peptide blocked the viral polymerase activity and growth of both virus types. Our findings provide proof of principle that protein-protein interaction inhibitors can be generated against influenza A and B viruses. Furthermore, this dual-binding peptide, combined with our novel screening method, is a promising platform to identify new antiviral lead compounds.

Given the discriminant dk of a quadratic field k, the number of cyclic relative extensions N\k of fixed odd prime degree p with dihedral absolute Galois group of order 2p , which share a common conductor /, is called the multiplicity of the dihedral discriminant d^ = f2^p~^d^ . In this paper, general formulas for multiplicities of dihedral discriminants are derived by analyzing the p-rank of the ring class group mod / of k . For the special case p = 3 , c4 = -3 , an elementary proof is given additionally. The theory is illustrated by a discussion of all known discriminants of multiplicity > 5 of totally real and complex cubic fields. Introduction Let p be an odd prime and AT|Q a cyclic extension of degree p. Then it is well known [9, 15, 7] that the conductor of K must have the form / = Pe 'Qi • ■ ■ It> where e = 0 or e = 2, /> 0, and the qi are pairwise distinct rational primes satisfying qi = X (mod p) for i = X, ... , t. The discriminant of K is just a power of the conductor, di( = fp~x . If, for any positive integer /, the number of cyclic extensions K\Q of degree p which share the same conductor / is denoted by m(f), then /-i/ p where p = dimF,(Qx(/)/Q* -qx(f)p) = dimr,(SyL, U(Z/fZ) ®Zp ¥p) = t + w with ®x(f) = {r£®x \(r,f) = X}, Q; = {reQx \r= X (mod*/)}, and w = \e. Moebius inversion yields an explicit formula for m(f): m(pe-qx---qt) = (p-l),+w-1 . It is the aim of the present paper to establish similar formulas for multiplicities of discriminants in the case of non-Galois extensions L|Q of degree p with dihedral normal closure yV of degree 2p. For the sake of illustration, the formulas are applied to discriminants with multiplicities up to 16 of non-Galois Received December 10, 1990; revised April 5, 1991. 1991 Mathematics Subject Classification. Primary 11R20, 11R11, 11R16.

Generally, p = 3 in all examples. The information about the 14 totally real cubic discriminants with multiplicities 4,6 has been taken from [10]. Data for the 69 complex cubic discriminants with multiplicities 6,9 has kindly been made available by the authors of [5] in personal communication. A common feature of all examples is that the 3-rank of the ring class group mod f of the quadratic field k is always p + t + w b(f) = 3, whence the sum of all partial multiplicities equals _(3P+t?+-5 1) = 13. Both parts (ws 1, denote by On the suborder Z H Zn (dk + w) of the maximal order Ok, where w = V/di. Then the unit group U(O,,) is exactly the intersection Uk n Q'X (n) .kn In the totally real case, the fundamental unit of k is denoted by q7. If p = 0, then the condition 7 E On, is certainly sufficient for d(n) = 0.

By means of a new criterion for higher multiplicities of additive representations of integers as sums of distinct terms of a fixed integer sequence sharp bounds are determined for the partition function of many sequences with the aid of a computer.