Egress of vaccinia virus from its host cell is mediated by the microtubule-associated motor kinesin-1, and three viral proteins, A36 and the F12/E2 complex, have been implicated in this process. Deletion of F12 expression causes a more severe reduction in egress than deletion of A36 but whether these proteins are involved in the same or different mechanisms of kinesin-1 recruitment is unknown. Here it is shown that a virus lacking both proteins forms a smaller plaque than mutants lacking either gene alone, indicating non-redundant functions. A36 not only links virions directly to kinesin-1 but also nucleates actin polymerization to propel surface virions away from the host cell. To address the relative importance of these functions for virus spread, a panel of recombinant viruses was constructed in which the ability of A36 to bind kinesin-1 or to nucleate actin polymerization was abrogated individually or together, in the presence or absence of F12 expression. Analysis of these viruses revealed that in the presence of the F12 protein, loss of kinesin-1 interaction made a greater contribution to plaque size than did the formation of actin tails. However in the absence of F12, the ability of A36 to promote egress was abrogated. Therefore, the ability of A36 to promote egress by kinesin-1 is reliant on the F12 protein.
Introduction
Young adult hip pain is increasingly recognized as an early warning sign for development of debilitating arthritis later in life. Two common causes for young adult hip pain are femoroacetabular impingement (FAI) and dysplasia. Yet, no universal referral pathway exists in the UK for young patients experiencing hip pain. Our aim was to investigate the timeline and journey of patients seen in a specialist young adult hip clinic at a tertiary orthopaedic centre.
Method
We conducted a case series using a two-part open question questionnaire given to 40 patients at a young adult hip clinic at a tertiary orthopaedic centre between March and November 2019.
Results
Average time from onset of symptoms to appointment in specialist clinic was 2.9 (± 3.9) years, with range between 1 month and 23 years. Average time between first GP appointment and appointment at a tertiary centre was 2.1 (±2.4) years. A total of 33 (83%) patients were seen in secondary care prior to referral to a specialist clinic at a tertiary centre. Imaging modalities prior to attendance were as follows: 23 (58%) patients had a hip X-ray, 15 (38%) a CT scan, 30 (75%) an MRI scan and 6 (15%) an ultrasound scan of their hip. A total of 23 (58%) patients had corticosteroid injections prior to referral to a specialist clinic.
Conclusions
Large variation seen in our results highlights an opportunity for service improvement and development of a universal referral pathway to improve patient care and reduce burden on other services.
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