Ph.D. Program in Cellular, Molecular and Industrial Biology
(Project n. 2: Functional Biology of Cellular and Molecular Systems)
Molecular basis of herpes simplex virus penetration into cells and control of virus-induced fusion
The mission of this laboratory is to elucidate the molecular bases of (i) herpes simplex virus (HSV) entry into the cells; and (ii) herpesvirus-induced fusion and its control. In 1998 the laboratory molecularly cloned Nectin1 as a novel member of a growing family of intercellular adhesion molecules, and identified it as the major HSV receptor. The receptor ligand is the viral glycoprotein D (gD). This laboratory has contributed to the identification of two functional domains in gD: an N-terminal receptor-binding site and a proline-rich membrane-proximal profusion domain, whose role is to trigger fusion. Fusion of the virion envelope with cell membranes is carried by the trio of the virion glycoproteins gB, gH, gL. In progress work demonstrates that the fusogenic glycoprotein is gH. In addition to promoting fusion, herpes simplex virus devotes a number of functions to tightly control fusion. This laboratory has shown that gB and the multiple spanning viral proteins gK and UL20 negatively control fusion induced by gD, gB, gH, gL.
Publications since 2001
- Cocchi F, Fusco D, Menotti L, Gianni T, Eisenberg RJ, Cohen GH, Campadelli-Fiume G. The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry. Proc Natl Acad Sci U S A. 2004 May 11;101(19):7445-50.
- Cocchi F, Menotti L, Di Ninni V, Lopez M, Campadelli-Fiume G. The herpes simplex virus JMP mutant enters receptor-negative J cells through a novel pathway independent of the known receptors nectin1, HveA, and nectin2. J Virol. 2004 May;78(9):4720-9.
- Bertucci C, Cimitan S, Menotti L. Optical biosensor analysis in studying herpes simplex virus glycoprotein D binding to target nectin1 receptor. J Pharm Biomed Anal. 2003 Aug 8;32(4-5):697-706.
- Avitabile E, Lombardi G, Campadelli-Fiume G. Herpes simplex virus glycoprotein K, but not its syncytial allele, inhibits cell-cell fusion mediated by the four fusogenic glycoproteins, gD, gB, gH, and gL. J Virol. 2003 Jun;77(12):6836-44.
- Zhou G, Avitabile E, Campadelli-Fiume G, Roizman B. The domains of glycoprotein D required to block apoptosis induced by herpes simplex virus 1 are largely distinct from those involved in cell-cell fusion and binding to nectin1. J Virol. 2003 Mar;77(6):3759-67.
- Menotti L, Cocchi F, Campadelli-Fiume G. Critical residues in the CC' ridge of the human nectin1 receptor V domain enable herpes simplex virus entry into the cell and act synergistically with the downstream region. Virology. 2002 Sep 15;301(1):6-12.
- Fabre S, Reymond N, Cocchi F, Menotti L, Dubreuil P, Campadelli-Fiume G, Lopez M. Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C-C'-C"-D beta-strands of the nectin1 V domain. J Biol Chem. 2002 Jul 26;277(30):27006-13.
- Menotti L, Casadio R, Bertucci C, Lopez M, Campadelli-Fiume G. Substitution in the murine nectin1 receptor of a single conserved amino acid at a position distal from the herpes simplex virus gD binding site confers high-affinity binding to gD. J Virol. 2002 Jun;76(11):5463-71.
- Cocchi F, Lopez M, Dubreuil P, Campadelli Fiume G, Menotti L. Free Full Text Chimeric nectin1-poliovirus receptor molecules identify a nectin1 region functional in herpes simplex virus entry. J Virol. 2001 Sep;75(17):7987-94.
- Lopez M, Cocchi F, Avitabile E, Leclerc A, Adelaide J, Campadelli-Fiume G, Dubreuil P. Free Full Text Novel, soluble isoform of the herpes simplex virus (HSV) receptor nectin1 (or PRR1-HIgR-HveC) modulates positively and negatively susceptibility to HSV infection. J Virol. 2001 Jun;75(12):5684-91.
- Menotti L, Avitabile E, Dubreuil P, Lopez M, Campadelli-Fiume G. Comparison of murine and human nectin1 binding to herpes simplex virus glycoprotein D (gD) reveals a weak interaction of murine nectin1 to gD and a gD-dependent pathway of entry. Virology. 2001 Apr 10;282(2):256-66.
Research Group
Prof. Gabriella Campadelli-Fiume (Responsabile)
e-mail: gabriella.campadelli@unibo.it
Dr. Elisa Avitabile (Ricercatore)
Dr. Laura Menotti (Ricercatore)
Dr. Tatiana Gianni (Dottorando)
Dr. Daniela Fusco (Dottorando)
Dr. Cristina Forghieri (Borsista)
Elisabetta Romagnoli (Collaboratore tecnico)
Location
Dipartimento di Patologia Sperimentale – Sezione di Microbiologia
e Virologia
Via S.Giacomo, 12 - 40126 Bologna Tel: +39 051 2094731; Fax : + 39 051
2094735
- http://patologia-sperimentale.unibo.it/
