GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:23460925

From GONUTS
Jump to: navigation, search
Citation

Lang, SM, Bynoe, MO, Karki, R, Tartell, MA and Means, RE (2013) Kaposi's Sarcoma-Associated Herpesvirus K3 and K5 Proteins Down Regulate Both DC-SIGN and DC-SIGNR. PLoS ONE 8:e58056

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of multicentric Castleman's disease, primary effusion lymphoma and Kaposi's sarcoma. In this study, we show that like the C-type lectin DC-SIGN, the closely related DC-SIGNR can also enhance KSHV infection. Following infection, they are both targeted for down modulation and our data indicate that the KSHV MARCH-family ubiquitin ligase K5 is mediating this regulation and subsequent targeting for degradation of DC-SIGN and DC-SIGNR in the context of the virus. The closely related viral K3 protein, is also able to target these lectins in exogenous expressions studies, but only weakly during viral infection. In addition to requiring a functional RING-CH domain, several protein trafficking motifs in the C-terminal region of both K3 and K5 are important in regulation of DC-SIGN and DC-SIGNR. Further exploration of this modulation revealed that DC-SIGN is endocytosed from the cell surface in THP-1 monocytes, but degraded from an internal location with minimal endocytosis in HEK-293 cells. Pull-down data indicate that both K3 and K5 preferentially associate with immature forms of the lectins, mediating their ubiquitylation and degradation. Together, these data emphasize the molecular complexities of K3 and K5, while expanding the repertoire of targets of these two viral proteins.

Links

PubMed PMC3584050 Online version:10.1371/journal.pone.0058056

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HHV8P:MIR1

GO:0039648: modulation by virus of host protein ubiquitination

ECO:0000315:

P

As demonstrated in Figure 7, DC-SIGN and DC-SIGNR are ubiquitylated when in the presence of K3 with an intact RING-CH domain.

complete
CACAO 6892

HHV8P:MIR1

GO:0039504: suppression by virus of host adaptive immune response

ECO:0000315:

P

See Figure 2. In the presence of wild-type K3, surface levels of MHC I were reduced about 80–90%. Figure 2 shows us that the levels of MHC 1 was greatly reduced with the addition of K3 and RING-CH mutated viral protein.

complete
CACAO 7033

HHV8P:MIR1

GO:0075509: viral entry into host cell via endocytosis

ECO:0000315:

P

Figure 4 demonstrates that Wild-Type K3 causes a decreased amount of endocytosis of DC-SIGNR, yet enhanced endocytosis of DC-SIGN.

complete
CACAO 7044

HHV8P:MIR1

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

See Figure 7. DC-SIGN and DC-SIGNR are ubiquitylated and degraded in a proteasomal- and lysosomal-dependent pathway by K3. It was confirmed that DC-SIGN displayed ubiquitylation only in the presence of K3 with an intact RING-CH domain.

complete
CACAO 7051

HHV8P:MIR1

involved_in

GO:0039504: suppression by virus of host adaptive immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR1

involved_in

GO:0039648: modulation by virus of host protein ubiquitination

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR1

involved_in

GO:0075509: endocytosis involved in viral entry into host cell

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR1

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR2

GO:0039648: modulation by virus of host protein ubiquitination

ECO:0000315:

P

As demonstrated in Figure 7, DC-SIGN and DC-SIGNR are ubiquitylated when in the presence of K5 with an intact RING-CH domain.

complete
CACAO 6891

HHV8P:MIR2

GO:0044078: positive regulation by symbiont of host receptor-mediated endocytosis

ECO:0000315:

P

As demonstrated by Figure 4C, in the presence of wildtype K5, a small but significant acceleration in endocytosis of DC-SIGN was detected

complete
CACAO 6893

HHV8P:MIR2

GO:0039504: suppression by virus of host adaptive immune response

ECO:0000315:

P

See Figure 2. In the presence of wild-type K5, surface levels of MHC I were reduced about 80–90%. Figure 2 shows us that the levels of MHC 1 was greatly reduced with the addition of K5 and RING-CH mutated viral protein.

complete
CACAO 7032

HHV8P:MIR2

GO:0075509: viral entry into host cell via endocytosis

ECO:0000315:

P

Figure 4 demonstrates that Wild-Type K5 causes a decreased amount of endocytosis of DC-SIGNR, yet enhanced endocytosis of DC-SIGN.

complete
CACAO 7043

HHV8P:MIR2

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

See Figure 7. DC-SIGN and DC-SIGNR are ubiquitylated and degraded in a proteasomal- and lysosomal-dependent pathway by K5. It was confirmed that DC-SIGN displayed ubiquitylation only in the presence of K5 with an intact RING-CH domain.

complete
CACAO 7050

HHV8P:MIR2

involved_in

GO:0039504: suppression by virus of host adaptive immune response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR2

involved_in

GO:0039648: modulation by virus of host protein ubiquitination

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR2

involved_in

GO:0006511: ubiquitin-dependent protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR2

involved_in

GO:0044078: positive regulation by symbiont of host receptor-mediated endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HHV8P:MIR2

involved_in

GO:0075509: endocytosis involved in viral entry into host cell

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.