A Systemic Receptor Network Triggered by Human cytomegalovirus Entry

Virus entry is a multistep process that triggers a variety of cellular pathways interconnecting into a complex network, yet the molecular complexity of this network remains largely unsolved. Here, by employing systems biology approach, we reveal a systemic virus-entry network initiated by human cytomegalovirus (HCMV), a widespread opportunistic pathogen. This network contains all known interactions and functional modules (i.e. groups of proteins) coordinately responding to HCMV entry. The number of both genes and functional modules activated in this network dramatically declines shortly, within 25 min post-infection. While modules annotated as receptor system, ion transport, and immune response are continuously activated during the entire process of HCMV entry, those for cell adhesion and skeletal movement are specifically activated during viral early attachment, and those for immune response during virus entry. HCMV entry requires a complex receptor network involving different cellular components, comprising not only cell surface receptors, but also pathway components in signal transduction, skeletal development, immune response, endocytosis, ion transport, macromolecule metabolism and chromatin remodeling. Interestingly, genes that function in chromatin remodeling are the most abundant in this receptor system, suggesting that global modulation of transcriptions is one of the most important events in HCMV entry. Results of in silico knock out further reveal that this entire receptor network is primarily controlled by multiple elements, such as EGFR (Epidermal Growth Factor) and SLC10A1 (sodium/bile acid cotransporter family, member 1). Thus, our results demonstrate that a complex systemic network, in which components coordinating efficiently in time and space contributes to virus entry.Comment: 26 page

Implications of Fermi-LAT observations on the origin of IceCube neutrinos

The IceCube (IC) collaboration recently reported the detection of TeV-PeV extraterrestrial neutrinos whose origin is yet unknown. By the photon-neutrino connection in $pp$ and $p\gamma$ interactions, we use the \fermi-LAT observations to constrain the origin of the IC detected neutrinos. We find that Galactic origins, i.e., the diffuse Galactic neutrinos due to cosmic ray (CR) propagation in the Milky Way, and the neutrinos from the Galactic point sources, may not produce the IC neutrino flux, thus these neutrinos should be of extragalactic origin. Moreover, the extragalactic gamma-ray bursts (GRBs) may not account for the IC neutrino flux, the jets of active galactic nuclei may not produce the IC neutrino spectrum, but the starburst galaxies (SBGs) may be promising sources. As suggested by the consistency between the IC detected neutrino flux and the Waxman-Bahcall bound, GRBs in SBGs may be the sources of both the ultrahigh energy, $>10^{19}$eV, CRs and the $1-100$~PeV CRs that produce the IC detected TeV-PeV neutrinos.Comment: JCAP accepted version; 8 pages, 2 figs; discussion on blazar origin added; conclusion unchange