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Adenovirus (Ad) membrane penetration during cell entry is poorly understood. Here we show that antibodies which neutralize the membrane lytic activity of the Ad capsid protein VI interfere with Ad endosomal membrane penetration. In vitro studies using a peptide corresponding to an N-terminal amphipathic alpha-helix of protein VI (VI-Phi), as well as other(More)
The structure of the adenovirus type 2 temperature-sensitive mutant 1 (Ad2ts1) was determined to a resolution of 10 A by cryo-electron microscopy single-particle reconstruction. Ad2ts1 was prepared at a nonpermissive temperature and contains the precursor forms of the capsid proteins IIIa, VI, and VIII; the core proteins VII, X (mu), and terminal protein(More)
A key step in adenovirus cell entry is viral penetration of cellular membranes to gain access to the cytoplasm and deliver the genome to the nucleus. Yet little is known about this important event in the adenoviral life cycle. Using the cytosolic protein galectin-3 (gal3) as a marker of membrane rupture with both live- and fixed-cell imaging, we demonstrate(More)
The identification of the adenovirus (AdV) protein that mediates endosome penetration during infection has remained elusive. Several lines of evidence from previous studies suggest that the membrane lytic factor of AdV is the internal capsid protein VI. While these earlier results imply a role for protein VI in endosome disruption, direct evidence during(More)
Adenovirus disrupts endosomal membranes during cell entry. The membrane lytic capsid protein VI (pVI) facilitates entry by fragmenting membranes. Although an N-terminal amphipathic α-helix (VI-Φ) possesses similar membrane affinity as pVI, truncated protein lacking VI-Φ (VIΔ54) still possesses moderate membrane affinity. We demonstrate that incorporation of(More)
x CHAPTER I: INTRODUCTION 1 COMPARISON OF ENVELOPED AND NONENVELOPED VIRUS ENTRY 1 NONENVELOPED VIRUS ENTRY 3 Traffic to site of membrane penetration 3 Release of the membrane lytic factor 4 Membrane penetration: pore formation and membrane fragmentation 5 Virus translocating across the limiting membrane 7 GALECTIN 3 AS A MARKER FOR VACUOLE LYSIS 8(More)
xv INTRODUCTION 1 CHAPTER ONE: LITERATURE REVIEW 5 The T lymphocyte in Immunology 5 Introduction 5 Establishing the role and function of Thymus 7 Delineation of two major lymphocyte subsets 8 Subdivision of T lymphocytes: CD4 and CD8 10 Heterogeneity of helper T cells 12 Introduction 12 Identification of Th1 and Th2 cells 12 Development and regulation of(More)
A complete understanding of herpesvirus morphogenesis requires studies of capsid assembly dynamics in living cells. Although fluorescent tags fused to the VP26 and pUL25 capsid proteins are available, neither of these components is present on the initial capsid assembly, the procapsid. To make procapsids accessible to live-cell imaging, we made a series of(More)
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