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0  structures 2  species 0  interactions 2  sequences 1  architecture

Family: Putative_CCL4 (PF17465)

Summary: Chemokine-like protein, HHV-6 U83 gene product

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Chemokine-like protein, HHV-6 U83 gene product Provide feedback

Human herpesvirus 6A (HHV-6A) and HHV-6B are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies [1]. HHV6 A/B encode two putative chemokine receptors and a chemokine-like protein. The HHV6 U83 gene encodes a CC chemokine, which functions as a highly selective and efficacious agonist for the human CCR2 receptor both in respect of signal transduction and the ability to induce chemotaxis. Homologues of the U83 gene products are found in Human cytomegalovirus encoded chemokines vCXC1 and vCXC2. HHV-6 CCL4 contains a region with the CC/CX3C chemokine motif and a glycosaminoglycan (GAG)-binding epitope, BBXB (B being a basic residue), found right before the third Cys residue, which very likely forms a disulfide bridge back to the first Cys of the protein [2]. This gene is the only HHV-6A/B divergent gene that is specific for these viruses. The U83 chemokine gene is distinct between HHV-6A and HHV-6B strains, encoding up to 13 % amino acid differences. The HHV-6A (U83A) and HHV-6B (U83B) chemokines have distinct specificities which determine chemoattraction or diversion of different leukocyte subsets for infection or immune evasion, thus an early component of cellular tropism as well as mediator of innate immunity. U83 also has a varied gene structure, with N-terminal length variation determining production of the encoded mature secreted chemokine, coupled with control by cell-directed splicing which truncates the chemokine gene early in replication to encode an antagonist. The ‘long’ active form of U83A has a unique broad specificity for receptors CCR1, CCR4, CCR5, CCR6 and CCR8 present on plasmacytoid and myeloid dendritic and monocyte/macrophage antigen presenting cells, as well as both TH1 and TH2 skin homing lymphocytes and NK cells; it is also amongst the highest affinity ligands for CCR5 and inhibits HIV-1 binding at this coreceptor. U83A can both block and divert human chemokine action while occupying the human chemokine receptors [3].

Literature references

  1. Staheli JP, Dyen MR, Deutsch GH, Basom RS, Fitzgibbon MP, Lewis P, Barcy S;, J Virol. 2016;90:6657-6674.: Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques. PUBMED:27170755 EPMC:27170755

  2. Luttichau HR, Clark-Lewis I, Jensen PO, Moser C, Gerstoft J, Schwartz TW;, J Biol Chem. 2003;278:10928-10933.: A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6. PUBMED:12554737 EPMC:12554737

  3. Tweedy J, Spyrou MA, Hubacek P, Kuhl U, Lassner D, Gompels UA;, J Gen Virol. 2015;96:370-389.: Analyses of germline, chromosomally integrated human herpesvirus 6A and B genomes indicate emergent infection and new inflammatory mediators. PUBMED:25355130 EPMC:25355130


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  Seed
(2)
Full
(2)
Representative proteomes UniProt
(30)
NCBI
(23)
Meta
(0)
RP15
(2)
RP35
(2)
RP55
(2)
RP75
(2)
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This family is new in this Pfam release.

Seed source: PRODOM:PD020168
Previous IDs: none
Type: Family
Author: El-Gebali S
Number in seed: 2
Number in full: 2
Average length of the domain: 97.00 aa
Average identity of full alignment: 86 %
Average coverage of the sequence by the domain: 100.00 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 210.5 210.4
Noise cut-off 21.7 19.1
Model length: 97
Family (HMM) version: 1
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