Novel infection of pericytes by Andes virus enhances endothelial cell permeability.

Andes Virus (ANDV) non-lytically infects pulmonary microvascular endothelial cells (PMECs) causing a severe capillary leak syndrome termed Hantavirus Pulmonary Syndrome (HPS). Basolaterally, PMECs are in contact with pericytes which play critical roles in regulating PMEC permeability and immune cell recruitment. We discovered that ANDV persistently infects primary human vascular pericytes for up to 9 days, and that PMEC monolayer permeability was increased by supernatants from ANDV-infected pericytes.

STAT3 imparts BRCAness by impairing homologous recombination repair in Epstein-Barr virus-transformed B lymphocytes.

Epstein-Barr virus (EBV) causes lymphomas and epithelial cell cancers. Though generally silent in B lymphocytes, this widely prevalent virus can cause endemic Burkitt lymphoma and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. By learning how EBV breaches barriers to cell proliferation, we hope to undermine those strategies to treat EBV lymphomas and potentially other cancers.

Novel replisome-associated proteins at cellular replication forks in EBV-transformed B lymphocytes.

Epstein-Barr virus (EBV) is an oncogenic herpesvirus and WHO class 1 carcinogen that resides in B lymphocytes of nearly all humans. While silent in most, EBV can cause endemic Burkitt lymphoma in children and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. The pathogenesis of such lymphomas is multifactorial but to a large extent depends on EBV's ability to aggressively drive cellular DNA replication and B cell proliferation despite cell-intrinsic barriers to replication.

Thy-1/CD90 a Bidirectional and Lateral Signaling Scaffold.

Thy-1/CD90 is a glycoprotein attached to the outer face of the plasma membrane with various functions, which depend on the context of specific physiological or pathological conditions. Many of these reported functions for Thy-1/CD90 arose from studies by our group, which identified the first ligand/receptor for Thy-1/CD90 as an integrin. This finding initiated studies directed toward unveiling the molecular mechanisms that operate downstream of Thy-1/CD90 activation, and its possible interaction with proteins in the membrane plane to regulate their function.

Intracellular Ca Increases and Connexin 43 Hemichannel Opening Are Necessary but Not Sufficient for Thy-1-Induced Astrocyte Migration.

Under pro-inflammatory conditions, astrocytes become reactive and acquire a migratory phenotype. Our results show that hemichannels formed by connexin 43 (Cx43) play an important role in Thy-1-induced astrocyte migration. The neuronal protein Thy-1 binds to αvβ3 integrin in astrocytes, thereby leading to intricate signaling pathways that include calcium (Ca) release from intracellular stores, opening of Cx43 hemichannels, release of ATP, activation of P2X7 receptor, and Ca influx.