Structures of the Hepaci-, Pegi-, and Pestiviruses envelope proteins suggest a novel membrane fusion mechanism.

Enveloped viruses encode specialised glycoproteins that mediate fusion of viral and host membranes. Discovery and understanding of the molecular mechanisms of fusion have been achieved through structural analyses of glycoproteins from many different viruses, and yet the fusion mechanisms of some viral genera remain unknown. We have employed systematic genome annotation and AlphaFold modelling to predict the structures of the E1E2 glycoproteins from 60 viral species in the Hepacivirus, Pegivirus, and Pestivirus genera. While the predicted structure of E2 varied widely, E1 exhibited a very consistent fold across genera, despite little or no similarity at the sequence level. Critically, the structure of E1 is unlike any other known viral glycoprotein. This suggests that the Hepaci-, Pegi-, and Pestiviruses may possess a common and novel membrane fusion mechanism. Comparison of E1E2 models from various species reveals recurrent features that are likely to be mechanistically important and sheds light on the evolution of membrane fusion in these viral genera. These findings provide new fundamental understanding of viral membrane fusion and are relevant to structure-guided vaccinology.

Occupational exposure to whole-body vibration and neck pain in the Swedish general population.

The primary aim of this study was to determine if occupational exposure to whole-body vibration (WBV) was associated with reporting neck pain. A cross-sectional study was conducted on a sample of the general population living in northern Sweden, aged 24-76 years. Data was retrieved through a digital survey that collected subjectively reported information on exposure to WBV and biomechanical exposures as well as neck pain. The study included 5,017 participants (response rate 44%). Neck pain was reported by 269 men (11.8%) and 536 women (20.2%). There was a statistically significant association between reporting occupational exposure to WBV half the time or more (adjusted OR 1.91; 95% CI 1.22-3.00) and reporting neck pain. In gender-stratified analyses, the same pattern was observed in men, while there were too few women to determine any association. We conclude that occupational exposure to whole-body vibration was associated with neck pain in men.Practitioner summary: This cross-sectional, survey-based study investigated associations between self-reported occupational whole-body vibration and neck pain. It showed significant associations between frequent exposure to whole-body vibration and neck pain among men but not women. In occupational health care settings, whole-body vibration could be considered as a possible risk factor for neck pain.

The association between cold exposure and musculoskeletal disorders: a prospective population-based study.

OBJECTIVES: The aim of the study was to determine the association between occupational ambient cold exposure and neck-shoulder pain (NSP), low back pain (LBP), and radiating LBP. METHODS: The study cohort comprised of 3,843 working subjects in northern Sweden who answered a baseline (spring 2015) and a follow-up questionnaire (spring 2021). NSP, LBP, and radiating LBP were assessed in both surveys. Occupational cold exposure was assessed at baseline, on a whole number numerical rating scale (NRS) and categorized in quartiles. Binary logistic regression determined the association between cold exposure at baseline and incident NSP, LBP, and radiating LBP, adjusted for age, gender, body mass index, smoking, mental stress, and physical workload. RESULTS: There were statistically significant associations between high occupational ambient cold exposure (NRS 5-7 and NRS 8-10) and NSP (1.59; 95% CI 1.08-2.33 and OR 1.50; 95% CI 1.03-2.19); NRS 8-10 and LBP (OR 1.61; 95% CI 1.13-2.29); and NRS 5-7 and radiating LBP (OR 1.87; 95% CI 1.12-3.16). Gender-stratified analyses showed statistically significant associations between high occupational ambient cold exposure (NRS 5-7 and NRS 8-10) and NSP (OR 1.97; 95% CI 1.07-3.61 and OR 1.97; 95% CI 1.06-3.67) for men and between NRS 8-10 and LBP (OR 1.82; 95% CI 1.14-2.91) and NRS 5-7 and radiating LBP (OR 2.20; 95% CI 1.15-4.24) for women. CONCLUSIONS: Occupational ambient cold exposure was associated with NSP, LBP, and radiating LBP, and should be recognised as a possible occupational risk factor.

Hourly Wages and Turnover of Community Health Workers According to US State Certification Policy and Medicaid Reimbursement, 2010-2021.

Objectives. To evaluate the effects of state community health worker (CHW) certification programs and Medicaid reimbursement for CHW services on wages and turnover. Methods. A staggered difference-in-differences design was used to compare CHWs in states with and without CHW certification or CHW Medicaid reimbursement policies. Data were derived from the 2010 to 2021 Current Population Survey in the United States. Results. CHW wages increased by $2.42 more per hour in states with certification programs than in states without programs (P = .04). Also, hourly wages increased more among White workers, men, and part-time workers (P = .04). Wages increased by $14.46 in the state with the earliest CHW certification program adoption (P < .01). Neither of the policies assessed had an effect on occupational turnover. Conclusions. CHW wages are higher in states with certification programs. However, wage gaps exist between Whites and non-Whites and between men and women. Public Health Implications. Federal, state, and employer-based strategies are needed to establish and sustain effective CHW programs to meet the needs of communities experiencing health and access disparities. (Am J Public Health. 2022;112(10):1480-1488. https://doi.org/10.2105/AJPH.2022.306965).

Ergonomists' experiences of executing occupational health surveillance for workers exposed to hand-intensive work: a qualitative exploration.

BACKGROUND: In order to reduce work-related upper limb disorders, the Swedish Work Environment Authority introduced an occupational health surveillance targeting hand-intensive work. A process model, aimed at supporting the employers as well as the occupational health service provider (i.e., ergonomist) in the work process with the occupational health surveillance, was developed. The objective of this qualitative study was to explore ergonomists' experiences of the execution of occupational health surveillance for hand-intensive work when following the novel process model as well as factors influencing the execution. METHODS: Semi-structured individual interviews were conducted with ten ergonomists on one occasion regarding their experience of following the work process. Qualitative content analysis with an inductive approach was used for analyzing the data. RESULTS: The ergonomists' experiences were summarized in one theme "A joint roadmap supporting a participatory process" and two categories "Clear structure provided by the components" and "The process influenced by collaboration and context". The ergonomists valued being guided by the systematics of the model, which provided structure and clarity in their work. Factors affecting the execution were related to communication deficiencies and uncertainties regarding expectations between different roles and functions (e.g., ergonomists and contact person, lack of information to workers). Additional factors, for instance, companies' routines and the ergonomist's intra-organizational support, such as access to IT-resources, could also affect the process. CONCLUSIONS: The findings reveal that this process model facilitates the ergonomists' work and cooperation with a client company. However, the process model needs to be developed and accompanied by a guideline with information related to the process, including e.g., description of a start-up meeting and of the roles/functions of the involved parties.

Occupational cold exposure and symptoms of carpal tunnel syndrome - a population-based study.

BACKGROUND: Cold exposure is an underrecognized occupational hazard that may increase the risk of peripheral nerve entrapment. The aim of this study was to determine if self-reported occupational exposure to contact and ambient cooling was associated with symptoms of carpal tunnel syndrome (CTS). METHODS: In this mainly cross-sectional study, surveys were conducted on a population-based sample of men and women between 18 and 70 years of age, living in northern Sweden. Cold exposure and presence of symptoms suggestive of CTS were subjectively reported. Associations between exposure and outcome were evaluated using logistic regression. RESULTS: The study included 2,703 women and 2,314 men, with a median age of 60 years (interquartile range 19). Symptoms of CTS were reported by 453 (9.2%). Being highly occupationally exposed (almost always) to contact cooling of the hands was associated with reporting CTS (OR 3.20; 95% CI 1.62-6.33), as was ambient cooling (OR 2.00; 95% CI 1.03-3.88) and severe ambient cooling (OR 4.02 95% CI 2.09-7.71), after adjusting for age, gender, body mass index, current daily smoking, diabetes mellitus, joint disease, and hand-arm vibration exposure. The point estimates increased with longer daily exposure duration. For workers exposed to severe ambient cooling for more than half of their working hours, in addition to performing heavy manual handling every day, the OR for reporting CTS was 7.25 (95% CI 3.88-13.53), with a positive additive interaction effect (expressed as relative excess risk due to interaction) of 4.67. CONCLUSIONS: Self-reported occupational exposure to contact and ambient cooling was associated with symptoms suggestive of CTS. There were statistically significant positive exposure-response patterns for time spent exposed to contact and ambient cooling at work in relation to reporting symptoms of CTS. Positive additive interaction effects between cold exposure and heavy manual handling were also found. Since there was important potential uncontrolled confounding regarding repetitive wrist movements and forceful gripping, the results need to be confirmed by other studies, preferably with longitudinal design and more detailed exposure assessment.

Patient and Community Health Worker Perceptions of Community Health Worker Clinical Integration.

Traditional community health workers (CHWs) are expanding their role into clinical settings (cCHW) to support patients with care coordination and advocacy services. We investigated the potential to integrate cCHWs, via evaluation of patients' and CHWs' key demographics, needs, and abilities. This mixed-methods study, including adult patients and CHWs, was conducted in the Inland Valley of Southern California, between 2016 and 2017. Survey data, key informant interviews, and focus group discussions were evaluated to compare patient/CHW core demographics, and contrast patient-identified healthcare needs against CHW-identified cCHW service capabilities. Quantitative data were evaluated descriptively and bi-variably using two-sample independent t tests and Pearson's Chi square tests. Qualitative data were coded for emerging themes using a priori and standard grounded theory methods. Patients and CHWs were significantly similar in age, education, and income, but significantly differed in gender, race, United States generation, and marital status. For all healthcare-related services in which patients and CHWs exhibited significant differences, the odds CHWs perceived themselves capable of performing services were greater than patients' stated need of services. Patients and CHWs overlapped regarding their expectations of cCHWs. Although patients and CHWs differed somewhat, they shared many of the same expectations for cCHW integration. This information is critical to further contextualize cCHW training programs and emphasizes the need to education patients about this exciting new form of healthcare delivery. The active role of cCHWs in the clinical care team and the community may expand patient access to preventive healthcare, improve care quality, and minimize health inequities.

Imaging regiospecific lipid turnover in mouse brain with desorption electrospray ionization mass spectrometry.

Compartmentalization of metabolism into specific regions of the cell, tissue, and organ is critical to life for all organisms. Mass spectrometric imaging techniques have been valuable in identifying and quantifying concentrations of metabolites in specific locations of cells and tissues, but a true understanding of metabolism requires measurement of metabolite flux on a spatially resolved basis. Here, we utilize desorption ESI-MS (DESI-MS) to measure lipid turnover in the brains of mice. We show that anatomically distinct regions of the brain have distinct lipid turnover rates. These turnover measurements, in conjunction with relative concentration, will enable calculation of regiospecific synthesis rates for individual lipid species in vivo. Monitoring spatially dependent changes in metabolism has the potential to significantly facilitate research in many areas, such as brain development, cancer, and neurodegeneration.

Does occupational health surveillance lead to risk reduction for workers exposed to hand-intensive work?

This mixed method study aimed to describe what risk-reducing actions were proposed by ergonomists after the execution of a guided process for occupational health surveillance for workers exposed to hand-intensive work in ten companies. Another aim was to describe the exposed workers' proposals for risk-reducing actions, including their perceptions of potential changes in the self-assessed exposure levels and work-related pain. Several actions, targeting organizational, technical, and/or individual measures were proposed. Proposals from the ergonomists more often targeted the personal measures, whereas the workers' proposals targeted technology or organizational changes. Six companies implemented at least one of the action proposals. These action proposals were not related to evaluation metrics, nor were they evaluated. This study indicates that both ergonomists and companies need guidance on how to improve to work in a participatory process for the implementation and evaluation of risk-reducing actions, e.g., by how to better include workers' experiences.

Occupational cold exposure is associated with upper extremity pain.

Background: Occupational cold exposure is common in Sweden but potential impacts on musculoskeletal disorders have not been thoroughly investigated. The primary aim of this study was to determine the associations between occupational contact and ambient cooling in relation to pain in the upper extremity. Methods: In this cross-sectional study, a digital survey was conducted on a population-based sample of women and men between 24 and 76 years of age, living in northern Sweden. Occupational cold exposure, heavy manual handling, work with vibrating tools as well as the presence of upper extremity pain at different sites were subjectively reported. Associations between exposure and outcome were evaluated using multiple binary logistic regression. Results: The final study sample included 2,089 (54.4%) women and 1,754 men, with a mean age of 56 years. Hand pain was reported by 196 (5.2%), lower arm pain by 144 (3.8%), and upper arm pain by 451 (11.9%). Severe ambient cooling for more than half of the working time was statistically significantly associated with hand pain (OR: 2.30; 95% CI: 1.23-4.29) and upper arm pain (OR: 1.57; 95% CI: 1.00-2.47) but not lower arm pain (OR: 1.87; 95% CI: 0.96-3.65) after adjusting for gender, age, body mass index, current daily smoking, heavy manual handling, and work with vibrating tools. Conclusions: Occupational cold exposure was statistically significantly associated with hand pain and upper arm pain. Therefore, occupational cold exposure should be recognized as a potential risk factor for musculoskeletal disorders in the upper extremity.

Surgery for subacromial impingement syndrome and occupational biomechanical risk factors in a 16-year prospective study among male construction workers.

OBJECTIVE: The aim of this study was to assess the association between occupational biomechanical exposures and the occurrence of surgical treatment for subacromial impingement syndrome (SIS). METHODS: A cohort of 220 295 male constructions workers who participated in a national occupational health surveillance program (1971-1993) were examined prospectively over a 16-year follow-up period (2001-2016) for surgically treated SIS. Worker job title, smoking status, height, weight, and age were registered on health examination. Job titles were mapped to 21 occupational groups based on tasks and training. A job exposure matrix (JEM) was developed with exposure estimates for each occupational group. Surgical cases were determined through linkage with the Swedish national in- and outpatient registers. Poisson regression was used to assess the relative risks (RR) for each biomechanical exposure. RESULTS: The total incidence rate of surgically treated SIS over the 16-year observation period was 201.1 cases per 100 000 person-years. Increased risk was evident for workers exposed to upper-extremity loading (push/pull/lift) (RR 1.45-2.30), high hand grip force (RR 1.47-2.23), using handheld tools (RR 1.52-2.09), frequent work with hands above shoulders (RR 1.62-2.11), static work (RR 1.77-2.26), and hand-arm vibration (RR 1.78-2.13). There was an increased risk for SIS surgery for all occupational groups (construction trades) compared with white-collar workers (RR 1.56-2.61). CONCLUSIONS: Occupational upper-extremity load and posture exposures were associated with increased risk for surgical treatment of SIS, which underlines the need for reducing workplace exposures and early symptom detection in highly exposed occupational groups.

Effects of Combining Occupationally Relevant Physical and Cognitive Tasks. A Systematic Review.

OBJECTIVES: Physical and cognitive tasks occur together in many occupations. Previous reviews of combined tasks have mainly focused on their effects in a sports context. This review investigated to which extent combinations (concurrent or alternating) of occupationally relevant physical and cognitive tasks influence responses reflecting biomechanical exposure, stress, fatigue, performance, and well-being. METHODS: We searched Scopus, Pubmed, Cinahl, and Psychinfo for controlled experiments investigating the effects of combinations of occupationally relevant physical and cognitive tasks in participants aged 18 to 70. In total, we identified 12 447 records. We added recent papers that had cited these studies (n = 573) to arrive at a total of 13 020 publications. After screening for relevance, 61 studies remained, of which 57 were classified to be of medium or high quality. Of the 57 studies, 51 addressed concurrent tasks, 5 alternating tasks, and 1 both concurrent and alternating tasks. RESULTS: Most studies of concurrent physical and cognitive tasks reported negative effects, if numerically small, on indicators of biomechanical exposure, fatigue, and performance, compared to a physical task alone. Results were mixed for stress indicators, and well-being was too little studied to justify any conclusions. Effects depended on the tasks, including their intensity and complexity. Alternating physical and cognitive tasks did not appear to influence outcomes much, compared to having passive breaks in-between physical tasks. CONCLUSIONS: The reviewed evidence indicated that concurrent physical and cognitive work tasks have negative, yet small effects on biomechanical indicators, fatigue and performance, compared to performing the physical task alone, but only if the physical task is intense, and the cognitive task is complex. Alternating between physical and cognitive tasks may have similar effects as breaking up physical tasks by passive breaks, but studies were few. Future studies should address ecologically valid combinations of physical and cognitive tasks, in particular in controlled field studies devoted to the long-term effects of combined work.

Propylene glycol inactivates respiratory viruses and prevents airborne transmission.

Viruses are vulnerable as they transmit between hosts, and we aimed to exploit this critical window. We found that the ubiquitous, safe, inexpensive and biodegradable small molecule propylene glycol (PG) has robust virucidal activity. Propylene glycol rapidly inactivates a broad range of viruses including influenza A, SARS-CoV-2 and rotavirus and reduces disease burden in mice when administered intranasally at concentrations commonly found in nasal sprays. Most critically, vaporised PG efficiently abolishes influenza A virus and SARS-CoV-2 infectivity within airborne droplets, potently preventing infection at levels well below those tolerated by mammals. We present PG vapour as a first-in-class non-toxic airborne virucide that can prevent transmission of existing and emergent viral pathogens, with clear and immediate implications for public health.

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.

Visiting the emergency department for dental problems: trends in utilization, 2001 to 2008.

OBJECTIVES: We tested the hypothesis that between 2001 and 2008, Americans increasingly relied upon emergency departments (EDs) for dental care. METHODS: Data from 2001 through 2008 were collected from the National Hospital Ambulatory Medical Care Survey (NHAMCS). Population-based visit rates for dental problems, and, for comparison, asthma, were calculated using annual US Census Bureau estimates. As part of the analysis, we described patient characteristics associated with large increases in ED dental utilization. RESULTS: Dental visit rates increased most dramatically for the following subpopulations: those aged 18 to 44 years (7.2-12.2 per 1000, P < .01); Blacks (6.0-10.4 per 1000, P < .01); and the uninsured (9.5-13.2 per 1000, P < .01). Asthma visit rates did not change although dental visit rates increased 59% from 2001 to 2008. CONCLUSIONS: There is an increasing trend in ED visits for dental issues, which was most pronounced among those aged 18 to 44 years, the uninsured, and Blacks. Dental visit rates increased significantly although there was no overall change in asthma visit rates. This suggests that community access to dental care compared with medical care is worsening over time.

Utility of a summative scale based on the Children with Special Health Care Needs (CSHCN) Screener to identify CSHCN with special dental care needs.

Our objective was to determine if a summative scale reflecting the number of positive criteria on the Children with Special Health Care Needs (CSHCN) Screener is useful in identifying subgroups of CSHCN at risk for poorer oral health and unmet dental care needs and who should be considered to have special dental care needs. Data were analyzed for a population-based sample of 91,642 US children <18 years from the 2007 National Survey of Children's Health. The independent variable of interest was the summative number of positive CSHCN Screener criteria. Dependent variables were parent-perceived condition of child's teeth, toothache, cavities, broken teeth, bleeding gums in the previous 6 months, and unmet dental care needs in the past 12 months. Descriptive and multivariable logistic regression analyses were performed for each outcome using the survey command in Stata to account for the sampling design. A summative scale based on the number of positive CSHCN Screener criteria was independently associated with various parent-perceived poorer oral health outcomes in children. CSHCN who met 4 or 5 screener criteria had 4 and 4.5 times, respectively, the odds of having fair-poor condition of teeth and bleeding gums relative to non-CSHCN. They also had 87% higher odds for parent-perceived toothache and 2 and 2.5 times the odds of having recent broken teeth and unmet dental care needs relative to non-CSHCN, respectively. There was no dose-dependent association between summative number of positive CSHCN Screener criteria and reported cavities in children. Application of a summative score based on the CSHCN Screener has utility in identifying the CSHCN subgroup with special dental care needs.

Validity of Three Survey Questions for Self-Assessed Sedentary Time.

Time spent in sedentary behavior (SB) has increased during the last decades. Accurate assessments are of importance when studying health consequences of SB. This study aimed to assess concurrent validity between three different questions for self-reported sitting and thigh worn accelerometer data. In total, 86 participants wore the ActivPAL accelerometer during three separate weeks, assessing sitting time with different questions each week. The questions used were Katzmarzyk, GIH stationary single-item question (SED-GIH), and a modified version of the single-item from IPAQ short form. In total 64, 57, and 55 participants provided valid accelerometer and questionnaire data at each time-point, respectively, and were included for analysis. Spearman and Pearson correlation was used to assess the validity. The three questions, Katzmarzyk, SED-GIH, and a modified question from IPAQ all showed a weak non-significant correlation to ActivPAL with r-values of 0.26, 0.25, and 0.19 respectively. For Katzmarzyk and SED-GIH, 50% and 37% reported correctly, respectively. For the modified IPAQ, 53% over-reported and 47% under-reported their sitting time. In line with previous research, our study shows poor validity for self-reported sitting-time. For future research, the use of sensor-based data on SB are of high importance.

Incorporating Oral Health into Pediatric Practice: National Trends 2008, 2012, 2018.

OBJECTIVE: Oral health is a critical component of children's overall health, but past research has found that pediatricians report barriers to implementing oral health into practice. Recently, policies have further delineated the importance of oral health in primary medical care. We sought to determine how pediatricians' practices and perceived barriers related to oral health involvement have changed since 2008. METHODS: There have been 3 nationally representative, cross-sectional, oral-health-focused periodic surveys of US American Academy of Pediatrics (AAP) members who provide health supervision: in 2008 (n = 1104; response rate (rr) = 69%), 2012 (n = 646; rr = 48%), and 2018 (n = 485; rr = 48%). The surveys asked about frequency of performing oral health tasks in children 3 years and younger, self-rated ability to perform these tasks, and attitudes about and barriers to oral health involvement. Predicted values from separate multivariable logistic regression models examined the independent effect of survey year. RESULTS: In 2018, pediatricians reported they were more likely to provide fluoride varnish and dental referrals at a younger age and less likely to complete a caries risk assessment or oral examination. They reported diminished barriers to incorporating oral health into pediatric practice. Other oral health activities, notably the oral screening examination and caries risk assessment, remain underutilized by pediatricians. CONCLUSIONS: From 2008 to 2018, more pediatricians reported performing a range of oral health tasks with fewer reported barriers. Ongoing efforts are needed to increase pediatricians' attention to oral screening examinations and caries risk assessments for all pediatric patients beginning in infancy, and to promote further use of fluoride varnish.

An entropic safety catch controls hepatitis C virus entry and antibody resistance.

E1 and E2 (E1E2), the fusion proteins of Hepatitis C Virus (HCV), are unlike that of any other virus yet described, and the detailed molecular mechanisms of HCV entry/fusion remain unknown. Hypervariable region-1 (HVR-1) of E2 is a putative intrinsically disordered protein tail. Here, we demonstrate that HVR-1 has an autoinhibitory function that suppresses the activity of E1E2 on free virions; this is dependent on its conformational entropy. Thus, HVR-1 is akin to a safety catch that prevents premature triggering of E1E2 activity. Crucially, this mechanism is turned off by host receptor interactions at the cell surface to allow entry. Mutations that reduce conformational entropy in HVR-1, or genetic deletion of HVR-1, turn off the safety catch to generate hyper-reactive HCV that exhibits enhanced virus entry but is thermally unstable and acutely sensitive to neutralising antibodies. Therefore, the HVR-1 safety catch controls the efficiency of virus entry and maintains resistance to neutralising antibodies. This discovery provides an explanation for the ability of HCV to persist in the face of continual immune assault and represents a novel regulatory mechanism that is likely to be found in other viral fusion machinery.

A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility.

The dynamic assembly and disassembly of membrane cytoskeleton junctional complexes is critical in cell migration. Here we describe a novel phosphorylation mechanism that regulates the hyaluronan receptor CD44. In resting cells, CD44 is constitutively phosphorylated at a single serine residue, Ser325. After protein kinase C is activated, a switch in phosphorylation results in CD44 being phosphorylated solely at an alternative residue, Ser291. Using fluorescence resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy (FLIM) and chemotaxis assays we show that phosphorylation of Ser291 modulates the interaction between CD44 and the cytoskeletal linker protein ezrin in vivo, and that this phosphorylation is critical for CD44-dependent directional cell motility.