HTLV-1 Evades Type I Interferon Antiviral Signaling by Inducing the Suppressor of Cytokine Signaling 1 (SOCS1)

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of Adult T cell Leukemia (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the majority of HTLV-1–infected individuals remain asymptomatic carriers (AC) during their lifetime, 2–5% will develop either ATL or HAM/TSP, but never both. To better understand the gene expression changes in HTLV-1-associated diseases, we examined the mRNA profiles of CD4+ T cells isolated from 7 ATL, 12 HAM/TSP, 11 AC and 8 non-infected controls. Using genomic approaches followed by bioinformatic analysis, we identified gene expression pattern characteristic of HTLV-1 infected individuals and particular disease states. Of particular interest, the suppressor of cytokine signaling 1—SOCS1—was upregulated in HAM/TSP and AC patients but not in ATL. Moreover, SOCS1 was positively correlated with the expression of HTLV-1 mRNA in HAM/TSP patient samples. In primary PBMCs transfected with a HTLV-1 proviral clone and in HTLV-1-transformed MT-2 cells, HTLV-1 replication correlated with induction of SOCS1 and inhibition of IFN-α/β and IFN-stimulated gene expression. Targeting SOCS1 with siRNA restored type I IFN production and reduced HTLV-1 replication in MT-2 cells. Conversely, exogenous expression of SOCS1 resulted in enhanced HTLV-1 mRNA synthesis. In addition to inhibiting signaling downstream of the IFN receptor, SOCS1 inhibited IFN-β production by targeting IRF3 for ubiquitination and proteasomal degradation. These observations identify a novel SOCS1 driven mechanism of evasion of the type I IFN antiviral response against HTLV-1

Fractures of the lateral condyle of the humerus in children

(East African Medical Journal 2001 78 (8): 424-429

FRACTURES OF THE LATERAL CONDYLE OF THE HUMERUS IN CHILDREN

Background: Conservative treatment of fractures of the lateral humeral condyle in childrenis associated with many problems as noted previously by several authors.Objective: To determine the outcome of internal fixation of fractures of the lateral hunieralcondyle.Design: A prospective study.Setting: Department of Orthopaedic Surgery, Asir Central Hospital, Abha, Saudi Arabia,befween 1991 and 1998.Subjects: Sixteen children with fracture of the lateral humeral condyle. All were admittedvia the Emergency Room and comprised 14 boys and two girls. Ages ranged between twoand 11 years.Interventions: All the patients had some form of internal fixation. Percutaneous KirsclhnerK- wire fixation was done for the undisplaced and minimally displaced fractures and openreduction and K-wire furation for the widely displaced and rotated fractures. One patientdeveloped non-union of the lateral condyle fracture that required bone grafting and internalfuration with lag screw.Main outcome measures: Enhancement of union and reduction of complications resultingfrom conservative treatment of the fractures.Results: Out of the sixteen cases, there was one case with a minor degree of mal-uniorn onaccount of loose K-wire and one case with non-union following open reduction andinternal fixation.Conclusion: The authors recommend internal furation of all fractures of the lateral humeralcondyle in children irrespective of the degree of displacement