A parapoxviral virion protein targets the retinoblastoma protein to inhibit NF-κB signaling.

Poxviruses have evolved multiple strategies to subvert signaling by Nuclear Factor κB (NF-κB), a crucial regulator of host innate immune responses. Here, we describe an orf virus (ORFV) virion-associated protein, ORFV119, which inhibits NF-κB signaling very early in infection (≤ 30 min post infection). ORFV119 NF-κB inhibitory activity was found unimpaired upon translation inhibition, suggesting that virion ORFV119 alone is responsible for early interference in signaling. A C-terminal LxCxE motif in ORFV119 enabled the protein to interact with the retinoblastoma protein (pRb) a multifunctional protein best known for its tumor suppressor activity. Notably, experiments using a recombinant virus containing an ORFV119 mutation which abrogates its interaction with pRb together with experiments performed in cells lacking or with reduced pRb levels indicate that ORFV119 mediated inhibition of NF-κB signaling is largely pRb dependent. ORFV119 was shown to inhibit IKK complex activation early in infection. Consistent with IKK inhibition, ORFV119 also interacted with TNF receptor associated factor 2 (TRAF2), an adaptor protein recruited to signaling complexes upstream of IKK in infected cells. ORFV119-TRAF2 interaction was enhanced in the presence of pRb, suggesting that ORFV119-pRb complex is required for efficient interaction with TRAF2. Additionally, transient expression of ORFV119 in uninfected cells was sufficient to inhibit TNFα-induced IKK activation and NF-κB signaling, indicating that no other viral proteins are required for the effect. Infection of sheep with ORFV lacking the ORFV119 gene led to attenuated disease phenotype, indicating that ORFV119 contributes to virulence in the natural host. ORFV119 represents the first poxviral protein to interfere with NF-κB signaling through interaction with pRb.

Giant Orf on the Nose.

Orf is a zoonotic infectious disease caused by parapoxvirus. Orf lesions are typically seen on the hand, but they have rarely been reported on the nose. Herein, the authors report a rare patient of an orf lesion on the nose of a 52-year-old man after the Muslim celebration of the feast of the sacrifice. The lesion spontaneously recovered 8 weeks after the initial appearance and showed no evidence of recurrence after 1 year of follow-up. Orf virus infections may occur more often after the celebration of the feast of the sacrifice in Muslim countries.

Isolation and characterization of an Indian ORF virus from goats.

Isolation and characterization of an orf virus has been described here. The virus was isolated from an outbreak of 'scabby mouth' in goats in Northern India. Viral morphology from the scab biopsy revealed typical ovoid-shaped particles characteristic of Parapoxvirus. Virus was isolated from sonicated scab suspension and characterized by restriction enzyme (RE) analysis and sequencing of full-length GM-CSF- and interleukin-2 inhibitory factor (GIF) gene. RE pattern of the virus did not show close resemblance to most of the orf viruses published earlier. However, it showed high sequence identity and closer phylogenetic relationship with previously published ORFV-SA00 strain, as evident from the nucleotide and deduced amino acid sequence of GIF gene.

A viral infection of the hand commonly seen after the feast of sacrifice: human orf (orf of the hand).

Orf of the hand is an uncommon zoonotic infection caused by a dermotropic DNA virus that belongs to the Parapoxvirus genus of the family Poxviridae. It is transmitted to humans through contact with infected sheep and goats and is reported as an occupational disease. We report nine cases of human orf seen in the hands of individuals, who were not occupationally exposed, after the feast of sacrifice in Turkey. Three cases were teachers and six out of the nine were housewives. We observed musculoskeletal complications and misdiagnoses. It is important to consider human orf in the differential diagnosis of hand lesions to prevent overtreatment and complications.

Rapidly growing cutaneous tumour of the right temple: Orf.

A typical lesion of orf developed on the temple of a 61-year-old man who apparently contracted the infection indirectly. In addition to the classical histological features of epidermal hyperplasia, necrosis, ballooning and vesical formation, the lesion also showed florid pseudoneoplastic vascular proliferation and a prominent component of eosinophils in the dermal inflammation.

Giant orf in a patient with chronic lymphocytic leukaemia.

A case of orf is presented in a patient with chronic lymphocytic leukaemia treated with chlorambucil and prednisone. Diagnosis was confirmed by electron microscopy and histopathology. Human orf is normally a self-limiting and benign condition but in this case the lesion grew to a size of 60 X 60 X 28 mm. When it was excised, local recurrence was treated with topical idoxuridine.

[Atopic dermatitis and pox-virus superinfections (author's transl)]. / Dermatite atopique et surinfection à pox-virus.

Subjects afflicted with atopic dermatitis are particularly predisposed to such viral superinfections as verruca, herpes (eczema herpeticum) and vaccinia (eczema vaccinatum). Knowledge of superinfection by the molluscum contagiosum virus is more recent and the authors describe one case. The orf virus (responsible for ovine ecthyma contagiosum), however, has never been described as responsible for the profuse superinfection of an atopic eczema. The authors observed one case of this in a child, atypical as result of his age (16 months), the cervical localization and the aspect, which was a telangiectasic granuloma type of the initial element, and finally of the satellization observed one week later. This child suffered from a generalized atopic eczema. Propagation of the orf lesions could have been favored by scratching, local corticoid treatment and by the deficit in cellular immunity observed in patient with atopic dermatitis. Indeed, viral superinfections, which are unusual by their profusion or their chronic nature, are often observed in immunodepressed subjects.