Analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection.

Simas, J. Pedro; Swann, D L; Bowden, Rory; Efstathiou, Stacey

doi:10.1099/0022-1317-80-1-75

Cited by 81 publications

(100 citation statements)

References 27 publications

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“…This alteration upon disruption of the M1 ORF was unexpected. Although both the M2 and M3 ORFs have been identified as regions of the genome that are transcriptionally active during latent infection, the M1 ORF has not been previously identified as a candidate latency-associated gene (11,22,36). The failure to detect M1 transcripts in the previous analyses may reflect the insufficient sensitivity of the assays employed.…”

Section: Discussionmentioning

confidence: 99%

Disruption of the Murine Gammaherpesvirus 68 M1 Open Reading Frame Leads to Enhanced Reactivation from Latency

Clambey

Virgin

Speck

2000

J Virol

139

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The gammaherpesviruses include the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV, or HHV-8) (for review, see references 10 and 18). These viruses establish lifelong infection of the host and are associated with a number of malignancies. To better understand gammaherpesvirus pathogenesis, we and others have begun to utilize infection of mice with murine gammaherpesvirus 68 (␥HV68, also referred to as MHV-68) (23, 37). ␥HV68 is a member of the gamma 2 -herpesvirus subfamily based on genome sequence (7,8,13,35).The pathogenesis of ␥HV68 has been reviewed recently (21,23,26,37). Briefly, ␥HV68 infection of inbred mice results in an acute, productive infection of multiple organs and a CD4 ϩ

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Section: Discussionmentioning

confidence: 99%

Disruption of the Murine Gammaherpesvirus 68 M1 Open Reading Frame Leads to Enhanced Reactivation from Latency

Clambey

Virgin

Speck

2000

J Virol

139

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“…MHV-68 M3 protein, encoded by early-late lytic gene, is expressed continually during lytic infection, during the establishment of latent infection, and during latency in vivo (Simas et al, 1999;Ebrahimi et al, 2003). M3 protein is predicted to play a role in the establishment of latency by indirect protection of latently infected B cells during lytic infection of macrophages and dendritic cells (Flaño et al, 2000;Marques et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties

Matuskova¹,

Pančík²,

Štibrániová³

et al. 2015

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Summary. -M3 protein of murine gammaherpesvirus 68 (MHV-68) was identifi ed as a viral chemokinebinding protein 3 (vCKBP-3) capable to bind a broad spectrum of chemokines and their receptors. During both acute and latent infection MHV-68 M3 protein provides a selective advantage for the virus by inhibiting the antiviral and infl ammatory response. A unique mutation Asp307Gly was identifi ed in the M3 protein of murine gammaherpesvirus 72 (MHV-72), localized near chemokine-binding domain. Study on chemokine-binding properties of MHV-72 M3 protein purifi ed from medium of infected cells implied reduced binding to some chemokines when compared to MHV-68 M3 protein. It was suggested that the mutation in the M3 protein might be involved in the attenuation of immune response to infection with MHV-72. Recently, Escherichia coli cells were used to prepare native recombinant M3 proteins of murine gammaherpesviruses 68 and 72 (Pančík et al., 2013). In this study, we assessed the chemokine-binding properties of three M3 proteins prepared in E. coli Rosetta-gami 2 (DE3) cells, the full length M3 protein of both MHV-68 and MHV-72 and MHV-68 M3 protein truncated in the signal sequence (the fi rst 24 aa). Th ey all displayed binding activity to human chemokines CCL5 (RANTES), CXCL8 (IL-8), and CCL3 (MIP-1α). Th e truncated MHV-68 M3 protein had more than twenty times reduced binding activity to CCL5, but only about fi ve and three times reduced binding to CXCL8 and CCL3 when compared to its full length counterpart. Binding of the full length MHV-72 M3 protein to all chemokines was reduced when compared to MHV-68 M3 protein. Its binding to CCL5 and CCL3 was reduced over ten and seven times. However, its binding to CXCL8 was only slightly reduced (64.8 vs 91.8%). Th ese data implied the signifi cance of the signal sequence and also of a single mutation (at aa 307) for effi cient M3 protein binding to some chemokines.

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“…1) (10,11). Initially, the ORF-74 gene product from Herpesvirus saimiri, ECRF3, was shown to bind interleukin-8 (IL-8) with high affinity even though it structurally is only distantly related to the mammalian IL-8 receptors, CXCR-1 and CXCR-2 (12).…”

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confidence: 99%

Agonists and Inverse Agonists for the Herpesvirus 8-encoded Constitutively Active Seven-transmembrane Oncogene Product, ORF-74

Rosenkilde

Kledal

Bräuner‐Osborne³

et al. 1999

Journal of Biological Chemistry

176

187

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A number of CXC chemokines competed with similar, nanomolar affinity against 125 I-interleukin-8 (IL-8) binding to ORF-74, a constitutively active seven-transmembrane receptor encoded by human herpesvirus 8. However, in competition against 125 I-labeled growth-related oncogene (GRO)-␣, the ORF-74 receptor was highly selective for GRO peptides, with IL-8 being 10,000-fold less potent. The constitutive stimulating activity of ORF-74 on phosphatidylinositol turnover was not influenced by, for example, IL-8 binding. In contrast, GRO peptides acted as potent agonists in stimulating ORF-74 signaling, whereas IP-10 and stromal cell-derived factor-1␣ surprisingly acted as inverse agonists. These peptides had similar pharmacological properties with regard to enhancing or inhibiting, respectively, the stimulatory effect of ORF-74 on NIH-3T3 cell proliferation. Construction of a high affinity zinc switch through introduction of two His residues at the extracellular end of transmembrane segment V enabled Zn 2؉ to act as a prototype non-peptide inverse agonist, which eliminated the constitutive signaling. It is concluded that ORF-74, which is believed to be causally involved in the formation of highly vascularized tumors, has been optimized for agonist and inverse agonist modulation by the endogenous angiogenic GRO peptides and angiostatic IP-10 and stromal cell-derived factor-1␣, respectively. ORF-74 could serve as a target for the development of non-peptide inverse agonist drugs as demonstrated by the effect of Zn 2؉ on the metal ion site-engineered receptor.

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Analysis of murine gammaherpesvirus-68 transcription during lytic and latent infection.

Abstract: Murine gammaherpesvirus-68 (MHV-68

Cited by 81 publications

References 27 publications

Disruption of the Murine Gammaherpesvirus 68 M1 Open Reading Frame Leads to Enhanced Reactivation from Latency

Disruption of the Murine Gammaherpesvirus 68 M1 Open Reading Frame Leads to Enhanced Reactivation from Latency

Soluble M3 proteins of murine gammaherpesviruses 68 and 72 expressed in Escherichia coli: analysis of chemokine-binding properties

Agonists and Inverse Agonists for the Herpesvirus 8-encoded Constitutively Active Seven-transmembrane Oncogene Product, ORF-74

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