Differential regulation of the attachment of Kaposi's sarcoma-associated herpesvirus (KSHV)-infected human B cells to extracellular matrix by KSHV-encoded gB and cellular alphaV integrins.
Kaposi's sarcoma-associated herpesvirus (KSHV) has two modes of replications: latent and lytic replications. Reactivation from latency is dictated, in part, by the cell cycle. Herein, we have attempted to delineate the importance of cell cycle in KSHV pathogenesis by exploring the expression pattern of cell-surface receptors during different phases of the cell cycle. alphaV integrin expression is augmented during S phase in fibroblasts, epithelial and KSHV-infected cells. Using a Matrigel system, we pioneer the concept that KSHV-infected primary effusion lymphoma cells can attach to extracellular matrix proteins. This attachment is mediated primarily via alphaV integrins or virally encoded gB, and occurs preferentially in cells from S phase or cells from S phase actively supporting a lytic infection respectively. Such an ability of infected B cells to attach to endothelial cells may also aid in the dissemination of infection. The keystone of this work is that for the first time, we describe the ability of KSHV-infected B cells to preferentially use cellular (alphaV) or viral (gB) receptors to specifically bind cells, depending upon the stage of the cell cycle and infection.
Dyson
Ossie F
OF
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Oxendine
Telisha L
TL
Hamden
Khalief E
KE
Ford
Patrick W
PW
Akula
Shaw M
SM
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology*; D002448:Cell Adhesion / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency; D014779:Virus Replication
D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D039564:Integrin alphaV; D007797:Laminin; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C059485:matrigel; D003094:Collagen