Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Identification of diverse database subsets using property-based and fragment-based molecular descriptions

This paper reports a comparison of calculated molecular properties and of 2D fragment bit-strings when used for the selection of structurally diverse subsets of a file of 44295 compounds. MaxMin dissimilarity-based selection and k-means cluster-based selection are used to select subsets containing between 1% and 20% of the file. Investigation of the numbers of bioactive molecules in the selected subsets suggest: that the MaxMin subsets are noticeably superior to the k-means subsets; that the property-based descriptors are marginally superior to the fragment-based descriptors; and that both approaches are noticeably superior to random selection

Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development

Experimental Demonstration of Fermi Surface Effects at Filling Factor 5/2

Using small wavelength surface acoustic waves (SAW) on ultra-high mobility heterostructures, Fermi surface properties are detected at 5/2 filling factor at temperatures higher than those at which the quantum Hall state forms. An enhanced conductivity is observed at 5/2 by employing sub 0.5 micron wavelength SAW, indicating a quasiparticle mean-free-path substantially smaller than that in the lowest Landau level. These findings are consistent with the presence of a filled Fermi sea of composite fermions, which may pair at lower temperatures to form the 5/2 ground state.Comment: 11 pages, 4 figure

Composite fermions in the Fractional Quantum Hall Effect: Transport at finite wavevector

We consider the conductivity tensor for composite fermions in a close to half-filled Landau band in the temperature regime where the scattering off the potential and the trapped gauge field of random impurities dominates. The Boltzmann equation approach is employed to calculate the quasiclassical transport properties at finite effective magnetic field, wavevector and frequency. We present an exact solution of the kinetic equation for all parameter regimes. Our results allow a consistent description of recently observed surface acoustic wave resonances and other findings.Comment: REVTEX, 4 pages, 1 figur

A Fermi Fluid Description of the Half-Filled Landau Level

We present a many-body approach to calculate the ground state properties of a system of electrons in a half-filled Landau level. Our starting point is a simplified version of the recently proposed trial wave function where one includes the antisymmetrization operator to the bosonic Laughlin state. Using the classical plasma analogy, we calculate the pair-correlation function, the static structure function and the ground state energy in the thermodynamic limit. These results are in good agreement with the expected behavior at $\nu=\frac12$.Comment: 4 pages, REVTEX, and 4 .ps file

Effective mass of composite fermion: a phenomenological fit in with anomalous propagation of surface acoustic wave

We calculate the conductivity associated with the anomalous propagation of a surface acoustic wave above a two-dimensional electron gas at $\nu=1/2$. Murthy-Shankar's middle representation is adopted and a contribution to the response functions beyond the random phase approximation has been taken into account. We give a phenomenological fit for the effective mass of composite fermion in with the experimental data of the anomalous propagation of surface acoustic wave at $\nu=1/2$ and find the phenomenological value of the effective mass is several times larger than the theoretical value $m_{th}^*=6\epsilon/e^2l_{1/2}$ derived from the Hartree-Fock approximation. We compare our phenomenologically fitting composite fermion effective mass with those appeared in the measurements of the activation energy and the Shubnikov-de Haas effect and find that our result is fairly reasonable.Comment: 8 pages, 5 figures, the longer version of cond-mat/9801131 with crucial corrections, accepted for publication by PR

Rapid Quantification of Molecular Diversity for Selective Database Acquisition

There is an increasing need to expand the structural diversity of the molecules investigated in lead-discovery programs. One way in which this can be achieved is by acquiring external datasets that will enhance an existing database. This paper describes a rapid procedure for the selection of external datasets using a measure of structural diversity that is calculated from sums of pairwise intermolecular structural similarities

Non-adiabatic scattering of a classical particle in an inhomogeneous magnetic field

We study the violation of the adiabaticity of the electron dynamics in a slowly varying magnetic field. We formulate and solve exactly a non-adiabatic scattering problem. In particular, we consider scattering on a magnetic field inhomogeneity which models scatterers in the composite-fermion theory of the half-filled Landau level. The calculated non-adiabatic shift of the guiding center is exponentially small and exhibits an oscillatory behavior related to the "self-commensurability" of the drifting cyclotron orbit. The analytical results are complemented with a numerical simulation.Comment: 4 pages REVTEX, 3 figures include

Dietary fat and cardiometabolic health: evidence, controversies, and consensus for guidance.

Although difficulties in nutrition research and formulating guidelines fuel ongoing debate, the complexities of dietary fats and overall diet are becoming better understood, argue Nita G Forouhi and colleague