Activation of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Lytic Replication by Human Cytomegalovirus

Vieira, Jeffrey; O’Hearn, Patricia M.; Kimball, Louise E.; Chandran, Bala; Corey, Lawrence

doi:10.1128/jvi.75.3.1378-1386.2001

Cited by 170 publications

(173 citation statements)

References 61 publications

Supporting

Mentioning

165

Contrasting

Unclassified

Order By: Relevance

“…The supernatant was next removed and centrifuged at 15,000 ϫ g for 4 h. The pellet was resuspended in one one-hundredth growth volume with complete media and centrifuged at 300 ϫ g for 5 min. The supernatant was then used for virus inoculation and stimulation (17,41). Real time PCR was performed to quantify the viral DNA.…”

Section: Methodsmentioning

confidence: 99%

“…BJAB is a line of KSHV and Epstein-Barr virus negative human B cells. These cell lines were grown as described previously (17,41 Cell Isolation-HMVECs were incubated with a rabbit or mouse anti-human VEGFR-3 antibody for 1 h. After washing with 1ϫ PBS, VEGFR-3-expressing cells were isolated using MACS colloidal superparamagnetic MicroBeads conjugated with goat anti-rabbit or goat anti-mouse IgG antibodies (Miltenyi Biotec Inc., Auburn, CA) according to the manufacturer's instructions. Isolated cells were cultured and expanded in the medium described above.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Zhang¹,

Wang²,

Chandran

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8) is the etiologic agent of Kaposi's sarcoma, an endothelial neoplasm. This ␥-herpesvirus encodes for several unique proteins that alter target cell function, including the virion envelope-associated glycoprotein B (gB). Glycoprotein B has an RGD (Arg-Gly-Asp) motif at the extracellular amino terminus region and binds to the ␣ 3 ␤ 1 surface integrin, which enhances virus entry. We now report that gB can activate the vascular endothelial growth factor receptor 3 (VEGFR-3) on the surface of microvascular endothelial cells and trigger receptor signaling, which can modulate endothelial migration and proliferation. Furthermore, we observed that VEGFR-3 expression and activation enhance KSHV infection and participate in KSHV-mediated transformation. These functional changes in the endothelium may contribute to the pathogenesis of Kaposi's sarcoma and suggest that interventions that inhibit gB activation of VEGFR-3 could be useful in the treatment of this neoplasm.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Zhang¹,

Wang²,

Chandran

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The latency program encodes numerous proteins that can affect cell survival and proliferation in vitro (8-12), whereas the lytic cycle encodes a variety of signaling proteins that can either directly mediate angiogenesis and inflammation (13-16) or induce expression of host proteins that can do likewise (17). In addition, KSHV latency is somewhat unstable, in that proliferating cells frequently give rise to uninfected segregants (A. Grundhoff and D.G., unpublished results); ongoing lytic infection also serves as a source of virus that can sustain the population of latently infected cells via de novo infection͞reinfection.In most cultured cells, the default pathway of KSHV infection is latency; that is, newly infected cells do not express the full lytic cascade, but rather maintain the viral DNA in the nucleus as a low copy number, circular episome whose expression is tightly restricted (18,19). Little is known about the mechanisms by which latency is established.…”

mentioning

confidence: 99%

“…In most cultured cells, the default pathway of KSHV infection is latency; that is, newly infected cells do not express the full lytic cascade, but rather maintain the viral DNA in the nucleus as a low copy number, circular episome whose expression is tightly restricted (18,19). Little is known about the mechanisms by which latency is established.…”

mentioning

confidence: 99%

Lytic but not latent infection by Kaposi's sarcoma-associated herpesvirus requires host CSL protein, the mediator of Notch signaling

Liang

Ganem

2003

Proc. Natl. Acad. Sci. U.S.A.

105

103

View full text Add to dashboard Cite

Infection by Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) isK aposi's sarcoma (KS), the most common neoplasm of untreated AIDS patients, is a complex lesion characterized by endothelial proliferation, neoangiogenesis, and inflammatory cell infiltration (1, 2). In 1994, a novel herpesvirus, now termed KS-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), was identified in KS lesions (3), and compelling epidemiological and molecular evidence strongly links KSHV infection to KS tumorigenesis (see refs. 4 and 5 for review). Like all herpesviruses, KSHV deploys two alternative genetic programs in infection: (i) latency, in which only a handful of viral genes is expressed and no infectious progeny are produced, and (ii) lytic infection, in which most viral genes are expressed in an ordered cascade, viral DNA is amplified, and infectious virions are released. Examination of KS biopsy specimens shows that KSHV infection is localized to the tumorous endothelial (spindle) cells (6), the majority of which are latently infected (7). A small subpopulation, however, are lytically infected (7), and recent evidence suggests that both latency and lytic infection contribute importantly to KS pathogenesis. The latency program encodes numerous proteins that can affect cell survival and proliferation in vitro (8-12), whereas the lytic cycle encodes a variety of signaling proteins that can either directly mediate angiogenesis and inflammation (13-16) or induce expression of host proteins that can do likewise (17). In addition, KSHV latency is somewhat unstable, in that proliferating cells frequently give rise to uninfected segregants (A. Grundhoff and D.G., unpublished results); ongoing lytic infection also serves as a source of virus that can sustain the population of latently infected cells via de novo infection͞reinfection.In most cultured cells, the default pathway of KSHV infection is latency; that is, newly infected cells do not express the full lytic cascade, but rather maintain the viral DNA in the nucleus as a low copy number, circular episome whose expression is tightly restricted (18,19). Little is known about the mechanisms by which latency is established. Formally speaking, the absence of lytic gene expression might be due to the absence of one or more positive regulators, or to the presence of active repression (or both).A single KSHV lytic-cycle viral gene (ORF50) controls the switch from latency to lytic replication (20,21). Its product, the replication and transcription activator (RTA), is a transcription factor that is both necessary (22) and sufficient (20,22,23) to trigger lytic reactivation. The mechanisms by which KSHV RTA acts have been extensively studied in cells transiently transfected by reporter gene constructs. RTA harbors a potent C-terminal activation domain, deletion of which results in a loss of transactivation activity (22,24). In addition, it has an N-terminal DNA-binding motif that can mediate sequence-specific DNA binding, and high-affinity sites for RTA recognition have been iden...

show abstract

“…Recently, it was suggested that KSHV may have a role in the development of primary pulmonary hypertension (14). KSHV can infect a variety of human cell types, including B, T, endothelial, epithelial, fibroblast, and keratinocyte cells, and nonhuman cell types, including owl monkey kidney and baby hamster kidney fibroblast cells (9,12,16,17,19,26,29,32,33,43,45,56,61).…”

mentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein K8.1 Is Dispensable for Virus Entry

Luna

Zhou

Baghian³

et al. 2004

J Virol

View full text Add to dashboard Cite

show abstract

Activation of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Lytic Replication by Human Cytomegalovirus

Cited by 170 publications

References 61 publications

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection

Lytic but not latent infection by Kaposi's sarcoma-associated herpesvirus requires host CSL protein, the mediator of Notch signaling

Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein K8.1 Is Dispensable for Virus Entry

Contact Info

Product

Resources

About