A third distinct tumor necrosis factor receptor of orthopoxviruses

Abstract

Cowpox virus Brighton red strain (CPV) contains a gene, crmD, which encodes a 320-aa tumor necrosis factor receptor (TNFR) of 44% and 22% identity, respectively, to the CPV TNFR-like proteins, cytokine response modifiers (crm) CrmB and CrmC. The crmD gene was interrupted in three other cowpox strains examined and absent in various other orthopoxviruses; however, four strains of ectromelia virus (ECT) examined contained an intact crmD (97% identity to CPV crmD) and lacked cognates of crmB and crmC. The protein, CrmD, contains a transport signal; a 151-aa cysteinerich region with 21 cysteines that align with human TNFRII ligand-binding region cysteines; and C-terminal region sequences that are highly diverged from cellular TNFR Cterminal region sequences involved in signal transduction. Bacterial maltose-binding proteins containing the CPV or ECT CrmD cysteine-rich region bound TNF and lymphotoxin-␣ (LT␣) and blocked their in vitro cytolytic activity. Secreted viral CrmD bound TNF and LT␣ and was detectable after the early stage of replication, using nonreducing conditions, as 60-to 70-kDa predominant and 90-to 250-kDa minor disulfide-linked complexes that were able to be reduced to a 46-kDa form and deglycosylated to a 38-kDa protein. Cells infected with CPV produced extremely low amounts of CrmD compared with ECT. Possessing up to three TNFRs, including CrmD, which is secreted as disulfide-linked complexes in varied amounts by CPV and ECT, likely enhances the dynamics of the immune modulating mechanisms of orthopoxviruses.

Vaccinia virus strains Lister, USSR and Evans express soluble and cell-surface tumour necrosis factor receptors.

“…and others 1998). On the other hand, CPV GRI-90 has four different TNFR-like genes (Shchelkunov et al, 1998), three of which express a vTNFR (Hu et al, 1994 ;Smith et al, 1996 ;Loparev et al, 1998). A soluble vTNFR has been predicted from sequence similarity in lymphocystis disease virus (Tidona & Darai, 1997), a large DNA iridovirus that infects fish, consistent with the conservation of TNF throughout evolution (Beck & Habicht, 1991).…”

“…CrmC is a 25 kDa protein that is expressed late during infection and binds TNF but not LTα (Smith et al, 1996). CrmD was identified recently in CPV and ectromelia virus and is a late, 46 kDa protein that is secreted as disulphide-linked complexes and binds TNF and LTα (Loparev et al, 1998). vTNFRs from myxoma virus (M-T2) and CPV (CrmC) bind TNF with high affinity and block TNF-mediated cytolysis in vitro (Schreiber et al, 1996 ;Smith et al, 1996).…”

A chemokine-binding domain in the tumor necrosis factor receptor from variola (smallpox) virus

“…1), was previously expressed from a bacterial vector and was shown to bind TNF (17). We expressed EV CrmD from VV Western Reserve, a strain that does not encode vTNFRs (20), and found that recombinant CrmD was secreted into the medium, bound human 125 I-TNF, and inhibited human TNF biological activity (Fig.…”

“…4 and 5; www.poxvirus.org). Cowpox virus (CPV), a rodent virus that infects other species sporadically, encodes all four vTNFRs (15)(16)(17)(18). Ectromelia virus (EV) is a highly virulent mouse pathogen that causes mousepox, a disease similar to smallpox, and encodes CrmD only (19).…”

Orf128蛋白在调节nf-Kb活化和逃逸宿主免疫的作用机制*

“…Published by New Century Science Press [20] 。另外，这个蛋白可以发挥 IκB 样区"替代品"的作用，以干扰 NF-κB 移位到细胞核 [21] 。牛痘病毒(CPXV)蛋白 CrmB、-C 和-D 能够作为可溶性的 TNF-α受体阻断配体和 受体的相互作用 [22][23][24][25] 。痘苗病毒 N1、A52R 和 B14 蛋白都有一个共同的类似 Bcl-2 的折叠结构，该结构可 抑制 IKK 复合物的活化 [26][27][28][29] ，而 M2L 蛋白可抑制 ERK2 和 K1L 阻止 IκBα的降解 [20] 。传染性软疣病毒所…”