PMID- 19234349
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20211020
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 50
IP  - 6
DP  - 2009 Jun
TI  - Role of nectin-1, HVEM, and PILR-alpha in HSV-2 entry into human retinal pigment 
      epithelial cells.
PG  - 2878-87
LID - 10.1167/iovs.08-2981 [doi]
AB  - PURPOSE: Herpes simplex virus-type 2 (HSV-2) can cause acute retinal necrosis 
      (ARN), which can lead to exudative and rhegmatogenous retinal detachment, yet 
      little is known about the cellular and molecular mechanisms of HSV-2 entry into 
      retinal pigment epithelial (RPE) cells. The goal of this study was to establish 
      the identity of the critical receptors used by the virus for infection. METHODS: 
      A reporter HSV-2 virus, which expresses beta-galactosidase, was used to quantify 
      entry into RPE cells, and viral replication was ascertained using a plaque assay. 
      Flow cytometry and immunocytochemistry were used to determine cellular expression 
      of entry receptors. Localization of these receptors to the apical or basal 
      surface of RPE cells was determined with immunocytochemistry. The necessity of 
      these receptors, individually and in combination, for viral entry was established 
      using receptor-specific antibodies and siRNAs. RESULTS: RPE cells are highly 
      susceptible to HSV-2 entry and replication. Several assays demonstrated the 
      expression of the entry receptors nectin-1, HVEM, and PILR-alpha and their 
      localization primarily to the apical surfaces of RPE cells. Receptor-specific 
      antibodies and siRNA knockdown of receptors significantly reduced viral entry and 
      implicated nectin-1 as an important receptor, with HVEM and PILR-alpha 
      potentially also contributing to entry. CONCLUSIONS: HSV-2 is capable of 
      developing a productive infection in RPE cells by using nectin-1 as an important 
      entry receptor. To lesser degrees, HVEM and PILR-alpha may also contribute to 
      HSV-2 entry into RPE cells.
FAU - Shukla, Shripaad Y
AU  - Shukla SY
AD  - Departments of Ophthalmology and Visual Sciences, College of Medicine, University 
      of Illinois at Chicago, Chicago, Illinois 60612, USA. dshukla@uic.edu
FAU - Singh, Yogesh K
AU  - Singh YK
FAU - Shukla, Deepak
AU  - Shukla D
LA  - eng
GR  - R01 AI057860/AI/NIAID NIH HHS/United States
GR  - P30 EY01792/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090221
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NECTIN1 protein, human)
RN  - 0 (Nectins)
RN  - 0 (PILRA protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Tumor Necrosis Factor, Member 14)
RN  - 0 (TNFRSF14 protein, human)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Adhesion Molecules/*physiology
MH  - Chlorocebus aethiops
MH  - Down-Regulation
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Gene Silencing/physiology
MH  - Herpesvirus 2, Human/*physiology
MH  - Humans
MH  - Membrane Glycoproteins/*physiology
MH  - Nectins
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Immunologic/*physiology
MH  - Receptors, Tumor Necrosis Factor, Member 14/*physiology
MH  - Retinal Pigment Epithelium/metabolism/*virology
MH  - Vero Cells
MH  - Viral Plaque Assay
MH  - Virus Replication/*physiology
PMC - PMC3686556
MID - NIHMS483249
EDAT- 2009/02/24 09:00
MHDA- 2009/06/12 09:00
PMCR- 2013/06/19
CRDT- 2009/02/24 09:00
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
PHST- 2013/06/19 00:00 [pmc-release]
AID - iovs.08-2981 [pii]
AID - 10.1167/iovs.08-2981 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2878-87. doi: 10.1167/iovs.08-2981. 
      Epub 2009 Feb 21.