Inhomogeneous scalar field solutions and inflation

We present new exact cosmological inhomogeneous solutions for gravity coupled to a scalar field in a general framework specified by the parameter $\lambda$. The equations of motion (and consequently the solutions) in this framework correspond either to low-energy string theory or Weyl integrable spacetime according to the sign of $\lambda$. We show that different inflationary behaviours are possible, as suggested by the study of the violation of the strong energy condition. Finally, by the analysis of certain curvature scalars we found that some of the solutions may be nonsingular.Comment: LaTex file, 14 page

Dust-filled axially symmetric universes with a cosmological constant

Following the recent recognition of a positive value for the vacuum energy density and the realization that a simple Kantowski-Sachs model might fit the classical tests of cosmology, we study the qualitative behavior of three anisotropic and homogeneous models: Kantowski-Sachs, Bianchi type-I and Bianchi type-III universes, with dust and a cosmological constant, in order to find out which are physically permitted. We find that these models undergo isotropization up to the point that the observations will not be able to distinguish between them and the standard model, except for the Kantowski-Sachs model $(\Omega_{k_{0}}0)$ with $\Omega_{\Lambda_{0}}$ smaller than some critical value $\Omega_{\Lambda_{M}}$. Even if one imposes that the Universe should be nearly isotropic since the last scattering epoch ($z\approx 1000$), meaning that the Universe should have approximately the same Hubble parameter in all directions (considering the COBE 4-Year data), there is still a large range for the matter density parameter compatible with Kantowsky-Sachs and Bianchi type-III if $|\Omega_0+\Omega_{\Lambda_0}-1|\leq \delta$, for a very small $\delta$ . The Bianchi type-I model becomes exactly isotropic owing to our restrictions and we have $\Omega_0+\Omega_{\Lambda_0}=1$ in this case. Of course, all these models approach locally an exponential expanding state provided the cosmological constant $\Omega_\Lambda>\Omega_{\Lambda_{M}}$.Comment: 12 pages, 9 figures, 1 table. Published in Physical Review D 1

Evolution of the Bianchi I, the Bianchi III and the Kantowski-Sachs Universe: Isotropization and Inflation

We study the Einstein-Klein-Gordon equations for a convex positive potential in a Bianchi I, a Bianchi III and a Kantowski-Sachs universe. After analysing the inherent properties of the system of differential equations, the study of the asymptotic behaviors of the solutions and their stability is done for an exponential potential. The results are compared with those of Burd and Barrow. In contrast with their results, we show that for the BI case isotropy can be reached without inflation and we find new critical points which lead to new exact solutions. On the other hand we recover the result of Burd and Barrow that if inflation occurs then isotropy is always reached. The numerical integration is also done and all the asymptotical behaviors are confirmed.Comment: 22 pages, 12 figures, Self-consistent Latex2e File. To be published in Phys. Rev.

Scalar fields in an anisotropic closed universe

We study in this article a class of homogeneous, but anisotropic cosmological models in which shear viscosity is included. Within the matter content we consider a component (the quintessence component) determined by the barotropic equations of state, $p=\alpha \rho$, with $\alpha < 0$. We establish conditions under which a closed axisymmetrical cosmological model may look flat al low redshift.Comment: 6 pages, Latex, 2 figures, accepted in Phys. Rev.

Bianchi Type I Cosmologies in Arbitrary Dimensional Dilaton Gravities

We study the low energy string effective action with an exponential type dilaton potential and vanishing torsion in a Bianchi type I space-time geometry. In the Einstein and string frames the general solution of the gravitational field equations can be expressed in an exact parametric form. Depending on the values of some parameters the obtained cosmological models can be generically divided into three classes, leading to both singular and nonsingular behaviors. The effect of the potential on the time evolution of the mean anisotropy parameter is also considered in detail, and it is shown that a Bianchi type I Universe isotropizes only in the presence of a dilaton field potential or a central deficit charge.Comment: REVTEX, 10 pages, 8 figure

Complementation of diverse HIV-1 Env defects through cooperative subunit interactions: a general property of the functional trimer

<p>Abstract</p> <p>Background</p> <p>The HIV-1 Env glycoprotein mediates virus entry by catalyzing direct fusion between the virion membrane and the target cell plasma membrane. Env is composed of two subunits: gp120, which binds to CD4 and the coreceptor, and gp41, which is triggered upon coreceptor binding to promote the membrane fusion reaction. Env on the surface of infected cells is a trimer consisting of three gp120/gp41 homo-dimeric protomers. An emerging question concerns cooperative interactions between the protomers in the trimer, and possible implications for Env function.</p> <p>Results</p> <p>We extended studies on cooperative subunit interactions within the HIV-1 Env trimer, using analysis of functional complementation between coexpressed inactive variants harboring different functional deficiencies. In assays of Env-mediated cell fusion, complementation was observed between variants with a wide range of defects in both the gp120 and gp41 subunits. The former included gp120 subunits mutated in the CD4 binding site or incapable of coreceptor interaction due either to mismatched specificity or V3 loop mutation. Defective gp41 variants included point mutations at different residues within the fusion peptide or heptad repeat regions, as well as constructs with modifications or deletions of the membrane proximal tryptophan-rich region or the transmembrane domain. Complementation required the defective variants to be coexpressed in the same cell. The observed complementation activities were highly dependent on the assay system. The most robust activities were obtained with a vaccinia virus-based expression and reporter gene activation assay for cell fusion. In an alternative system involving Env expression from integrated provirus, complementation was detected in cell fusion assays, but not in virus particle entry assays.</p> <p>Conclusion</p> <p>Our results indicate that Env function does not require every subunit in the trimer to be competent for all essential activities. Through cross-talk between subunits, the functional determinants on one defective protomer can cooperatively interact to trigger the functional determinants on an adjacent protomer(s) harboring a different defect, leading to fusion. Cooperative subunit interaction is a general feature of the Env trimer, based on complementation activities observed for a highly diverse range of functional defects.</p

Prediction of HIV-1 virus-host protein interactions using virus and host sequence motifs

<p>Abstract</p> <p>Background</p> <p>Host protein-protein interaction networks are altered by invading virus proteins, which create new interactions, and modify or destroy others. The resulting network topology favors excessive amounts of virus production in a stressed host cell network. Short linear peptide motifs common to both virus and host provide the basis for host network modification.</p> <p>Methods</p> <p>We focused our host-pathogen study on the binding and competing interactions of HIV-1 and human proteins. We showed that peptide motifs conserved across 70% of HIV-1 subtype B and C samples occurred in similar positions on HIV-1 proteins, and we documented protein domains that interact with these conserved motifs. We predicted which human proteins may be targeted by HIV-1 by taking pairs of human proteins that may interact via a motif conserved in HIV-1 and the corresponding interacting protein domain.</p> <p>Results</p> <p>Our predictions were enriched with host proteins known to interact with HIV-1 proteins ENV, NEF, and TAT (p-value < 4.26E-21). Cellular pathways statistically enriched for our predictions include the T cell receptor signaling, natural killer cell mediated cytotoxicity, cell cycle, and apoptosis pathways. Gene Ontology molecular function level 5 categories enriched with both predicted and confirmed HIV-1 targeted proteins included categories associated with phosphorylation events and adenyl ribonucleotide binding.</p> <p>Conclusion</p> <p>A list of host proteins highly enriched with those targeted by HIV-1 proteins can be obtained by searching for host protein motifs along virus protein sequences. The resulting set of host proteins predicted to be targeted by virus proteins will become more accurate with better annotations of motifs and domains. Nevertheless, our study validates the role of linear binding motifs shared by virus and host proteins as an important part of the crosstalk between virus and host.</p

Rab7A Is Required for Efficient Production of Infectious HIV-1

Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle

HIV-1 assembly in macrophages

The molecular mechanisms involved in the assembly of newly synthesized Human Immunodeficiency Virus (HIV) particles are poorly understood. Most of the work on HIV-1 assembly has been performed in T cells in which viral particle budding and assembly take place at the plasma membrane. In contrast, few studies have been performed on macrophages, the other major target of HIV-1. Infected macrophages represent a viral reservoir and probably play a key role in HIV-1 physiopathology. Indeed macrophages retain infectious particles for long periods of time, keeping them protected from anti-viral immune response or drug treatments. Here, we present an overview of what is known about HIV-1 assembly in macrophages as compared to T lymphocytes or cell lines

Topology of the C-Terminal Tail of HIV-1 gp41: Differential Exposure of the Kennedy Epitope on Cell and Viral Membranes

The C-terminal tail (CTT) of the HIV-1 gp41 envelope (Env) protein is increasingly recognized as an important determinant of Env structure and functional properties, including fusogenicity and antigenicity. While the CTT has been commonly referred to as the “intracytoplasmic domain” based on the assumption of an exclusive localization inside the membrane lipid bilayer, early antigenicity studies and recent biochemical analyses have produced a credible case for surface exposure of specific CTT sequences, including the classical “Kennedy epitope” (KE) of gp41, leading to an alternative model of gp41 topology with multiple membrane-spanning domains. The current study was designed to test these conflicting models of CTT topology by characterizing the exposure of native CTT sequences and substituted VSV-G epitope tags in cell- and virion-associated Env to reference monoclonal antibodies (MAbs). Surface staining and FACS analysis of intact, Env-expressing cells demonstrated that the KE is accessible to binding by MAbs directed to both an inserted VSV-G epitope tag and the native KE sequence. Importantly, the VSV-G tag was only reactive when inserted into the KE; no reactivity was observed in cells expressing Env with the VSV-G tag inserted into the LLP2 domain. In contrast to cell-surface expressed Env, no binding of KE-directed MAbs was observed to Env on the surface of intact virions using either immune precipitation or surface plasmon resonance spectroscopy. These data indicate apparently distinct CTT topologies for virion- and cell-associated Env species and add to the case for a reconsideration of CTT topology that is more complex than currently envisioned