Cell membrane-bound Kaposi's sarcoma-associated herpesvirus-encoded glycoprotein B promotes virus latency by regulating expression of cellular Egr-1.
One of the important questions in the field of virus research is about the balance between latent and lytic cycles of replication. Kaposi's sarcoma-associated herpesvirus (KSHV) remains predominantly in a latent state, with only 1-3% of cells supporting a lytic replication at any time. KSHV glycoprotein B (gB) is expressed not only on the virus envelope but also on the surfaces of the few cells supporting lytic replication. Using co-culture experiments, we determined that expression of KSHV gB on as few as 1-2% of human dermal microvascular endothelial cells resulted in a 10-fold inhibition of expression of ORF50, a viral gene critical for the onset of lytic replication. Also, we demonstrate that such a profound inhibitory effect of gB on the lytic cycle of virus replication is by repressing the ability of Egr-1 (early growth response-1) to bind and activate the ORF50 promoter. In general, virus-encoded late stage structural proteins, such as gB, are said to play major roles in virus entry and egress. The present report provides initial evidence supporting a role for membrane-associated gB expressed in a minimal number of cells to promote virus latency. These findings may have ramifications leading to a better understanding of the role of virus-encoded structural proteins not only in KSHV-related diseases but also in other viruses causing latent infections.
Dyson
Ossie F
OF
Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA.
Traylen
Christopher M
CM
Akula
Shaw M
SM
D002462:Cell Membrane / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D004277:DNA, Single-Stranded / Q000235:genetics* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D012514:Sarcoma, Kaposi / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency
C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D014759:Viral Envelope Proteins; C116207:glycoprotein B, human herpesvirus 8