PMID- 12042810 OWN - NLM STAT- MEDLINE DCOM- 20020626 LR - 20220330 IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 8 IP - 6 DP - 2002 Jun TI - Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. PG - 594-9 AB - Epstein-Barr virus is ubiquitous and is causally implicated in lymphoid and epithelial malignancies. Virus invades oropharyngeal mucosa and establishes latency in B lymphocytes. Reactivating lymphocytes shed virus into saliva for spread to new hosts. A complex of three virus glycoproteins, gH, gL and gp42, is essential for entry. B-cell entry requires binding of gp42 to human leukocyte antigen (HLA) class II whereas entry into epithelial cells lacking HLA class II requires complexes without gp42. To accommodate infection of each, the virus carries both three-part and two-part complexes. We show here that HLA class II in the virus-producing cell alters the ratio of three-part to two-part complexes. As a consequence, virus originating in epithelial cells efficiently infects B cells whereas B-cell derived virus better infects epithelial cells. This molecular switch is a novel strategy that could alter tropism of virus from epithelium to B cells and then back to epithelium in a new host. FAU - Borza, Corina M AU - Borza CM AD - School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA. borzac@umkc.edu FAU - Hutt-Fletcher, Lindsey M AU - Hutt-Fletcher LM LA - eng GR - R01-AI20662/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 0 (DNA, Viral) RN - 0 (Histocompatibility Antigens Class II) RN - EC 2.7.1.21 (Thymidine Kinase) SB - IM CIN - Nat Med. 2002 Jun;8(6):559-60. PMID: 12042800 MH - Animals MH - B-Lymphocytes/immunology/*virology MH - Cell Line MH - DNA, Viral/analysis MH - Epithelial Cells/immunology/*virology MH - Gene Deletion MH - Herpesvirus 4, Human/genetics/*physiology MH - Histocompatibility Antigens Class II/analysis MH - Lymphocyte Activation MH - Thymidine Kinase/deficiency/genetics MH - Virus Replication/*physiology MH - Virus Shedding EDAT- 2002/06/04 10:00 MHDA- 2002/06/27 10:01 CRDT- 2002/06/04 10:00 PHST- 2002/06/04 10:00 [pubmed] PHST- 2002/06/27 10:01 [medline] PHST- 2002/06/04 10:00 [entrez] AID - nm0602-594 [pii] AID - 10.1038/nm0602-594 [doi] PST - ppublish SO - Nat Med. 2002 Jun;8(6):594-9. doi: 10.1038/nm0602-594.