Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

Atlantic Salmon Reovirus Infection Causes a CD8 T Cell Myocarditis in Atlantic Salmon (Salmo salar L.)

Heart and skeletal inflammation (HSMI) of farmed Atlantic salmon (Salmo salar L.) is a disease characterized by a chronic myocarditis involving the epicardium and the compact and spongious part of the heart ventricle. Chronic myositis of the red skeletal muscle is also a typical finding of HSMI. Piscine reovirus (PRV) has been detected by real-time PCR from farmed and wild salmon with and without typical changes of HSMI and thus the causal relationship between presence of virus and the disease has not been fully determined [1]. In this study we show that the Atlantic salmon reovirus (ASRV), identical to PRV, can be passaged in GF-1 cells and experimental challenge of naïve Atlantic salmon with cell culture passaged reovirus results in cardiac and skeletal muscle pathology typical of HSMI with onset of pathology from 6 weeks, peaking by 9 weeks post challenge. ASRV replicates in heart tissue and the peak level of virus replication coincides with peak of heart lesions. We further demonstrate mRNA transcript assessment and in situ characterization that challenged fish develop a CD8+ T cell myocarditis

Interstellar Matter and the Boundary Conditions of the Heliosphere

The interstellar cloud surrounding the solar system regulates the galactic environment of the Sun, and determines the boundary conditions of the heliosphere. Both the Sun and interstellar clouds move through space, so these boundary conditions change with time. Data and theoretical models now support densities in the cloud surrounding the solar system of n(HI)=0.22+/-0.06 cm^-3, and n(e-)~0.1 cm-3, with larger values allowed for n(HI) by radiative transfer considerations. Ulysses and Extreme Ultraviolet Explorer satellite HeI data yield a cloud temperature of 6,400 K. Nearby interstellar gas appears to be structured and inhomogeneous. The interstellar gas in the Local Fluff cloud complex exhibits elemental abundance patterns in which refractory elements are enhanced over the depleted abundances found in cold disk gas. Within a few parsecs of the Sun, inconclusive evidence for factors of 2--5 variation in MgII and FeII gas phase abundances is found, providing evidence for variable grain destruction. Observations of the hydrogen pile-up at the nose of the heliosphere are consistent with a barely subsonic motion of the heliosphere with respect to the surrounding interstellar cloud. Uncertainties on the velocity vector of the cloud that surrounds the solar system indicate that it is uncertain as to whether the Sun and alpha Cen are or are not immersed in the same interstellar cloud.Comment: 24 pages 3 figure