66 research outputs found
Paramyxovirus Sendai virus-like particle formation by expression of multiple viral proteins and acceleration of its release by C protein
AbstractEnvelope viruses maturate by macromolecule assembly and budding. To investigate these steps, we generated virus-like particles (VLPs) by co-expression of structural proteins of Sendai virus (SeV), a prototype of the family Paramyxoviridae. Simultaneous expression of matrix (M), nucleo- (N), fusion (F), and hemagglutinin-neuraminidase (HN) proteins resulted in the generation of VLPs that had morphology and density similar to those of authentic virus particles, although the efficiency of release from cells was significantly lower than that of the virus. By using this VLP formation as a model of virus budding, roles of individual proteins in budding were investigated. The M protein was a driving force of budding, and the F protein facilitated and the HN protein suppressed VLP release. Either of the glycoproteins, F or HN, as well as the N protein, significantly shifted density of VLPs to that of virus particles, suggesting that viral proteins bring about integrity of VLPs by protein–protein interactions. We further found that co-expression of a nonstructural protein, C, but not V, enhanced VLP release to a level comparable to that of virus particles, demonstrating that the C protein plays a role in virus budding
MDM2 is a novel E3 ligase for HIV-1 Vif
The human immunodeficiency virus type 1 (HIV-1) Vif plays a crucial role in the viral life cycle by antagonizing a host restriction factor APOBEC3G (A3G). Vif interacts with A3G and induces its polyubiquitination and subsequent degradation via the formation of active ubiquitin ligase (E3) complex with Cullin5-ElonginB/C. Although Vif itself is also ubiquitinated and degraded rapidly in infected cells, precise roles and mechanisms of Vif ubiquitination are largely unknown. Here we report that MDM2, known as an E3 ligase for p53, is a novel E3 ligase for Vif and induces polyubiquitination and degradation of Vif. We also show the mechanisms by which MDM2 only targets Vif, but not A3G that binds to Vif. MDM2 reduces cellular Vif levels and reversely increases A3G levels, because the interaction between MDM2 and Vif precludes A3G from binding to Vif. Furthermore, we demonstrate that MDM2 negatively regulates HIV-1 replication in non-permissive target cells through Vif degradation. These data suggest that MDM2 is a regulator of HIV-1 replication and might be a novel therapeutic target for anti-HIV-1 drug
The Quiescent Intracluster Medium in the Core of the Perseus Cluster
Clusters of galaxies are the most massive gravitationally-bound objects in
the Universe and are still forming. They are thus important probes of
cosmological parameters and a host of astrophysical processes. Knowledge of the
dynamics of the pervasive hot gas, which dominates in mass over stars in a
cluster, is a crucial missing ingredient. It can enable new insights into
mechanical energy injection by the central supermassive black hole and the use
of hydrostatic equilibrium for the determination of cluster masses. X-rays from
the core of the Perseus cluster are emitted by the 50 million K diffuse hot
plasma filling its gravitational potential well. The Active Galactic Nucleus of
the central galaxy NGC1275 is pumping jetted energy into the surrounding
intracluster medium, creating buoyant bubbles filled with relativistic plasma.
These likely induce motions in the intracluster medium and heat the inner gas
preventing runaway radiative cooling; a process known as Active Galactic
Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus
cluster core, which reveal a remarkably quiescent atmosphere where the gas has
a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from
the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s
is found across the 60 kpc image of the cluster core. Turbulent pressure
support in the gas is 4% or less of the thermodynamic pressure, with large
scale shear at most doubling that estimate. We infer that total cluster masses
determined from hydrostatic equilibrium in the central regions need little
correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July
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