Tissue-Resident Memory CD4+ T Cells Play a Dominant Role in the Initiation of Antitumor Immunity.

Tumor immunology has been studied extensively. Tumor immunology-based cancer immunotherapy has become one of the most promising approaches for cancer treatment. However, one of the fundamental aspects of tumor immunology-the initiation of antitumor immunity-is not fully understood. Compared to that of CD8+ T cells, the effect of CD4+ T cells on antitumor immunity has not been fully appreciated. Using a gene knockout mouse model, the mice of which are deficient in the TCRα repertoire, specifically lacking invariant NKT and mucosal-associated invariant T cells, we found that the deficiency in TCRα repertoire diversity did not affect the antitumor immunity, at least to B16BL6 melanoma and EO771 breast cancer. However, after acquiring thymocytes or splenocytes from wild-type mice, these knockout mice exhibited greatly enhanced and long-lasting antitumor immunity. This enhanced antitumor immunity depended on CD4+ T cells, especially CD4+ tissue-resident memory T (TRM) cells, but not invariant NKT or CD8+ T cells. We also present evidence that CD4+ TRM cells initiate antitumor immunity through IFN-γ, and the process is dependent on NK cells. The CD4+ TRM/NK axis appears to control tumor formation and development by eliminating tumor cells and modulating the tumor microenvironment. Taken together, our results demonstrated that CD4+ TRM cells play a dominant role in the initiation of antitumor immunity.

Chronic Alcohol Consumption Enhances Skeletal Muscle Wasting in Mice Bearing Cachectic Cancers: The Role of TNFα/Myostatin Axis.

BACKGROUND: Chronic alcohol consumption enhances cancer-associated cachexia, which is one of the major causes of decreased survival. The precise molecular mechanism of how alcohol consumption enhances cancer-associated cachexia, especially skeletal muscle loss, remains to be elucidated. METHODS: We used a mouse model of chronic alcohol consumption, in which 20% (w/v) alcohol was provided as sole drinking fluid, and Lewis lung carcinoma to study the underlying mechanisms. RESULTS: We found that alcohol consumption up-regulated the expression of MAFbx, MuRF-1, and LC3 in skeletal muscle, suggesting that alcohol enhanced ubiquitin-mediated proteolysis and LC3-mediated autophagy. Alcohol consumption enhanced phosphorylation of Smad2/3, p38, and ERK and decreased the phosphorylation of FOXO1. These are the signaling molecules governing protein degradation pathways. Moreover, alcohol consumption slightly up-regulated the expression of insulin receptor substrate-1, did not affect phosphatidylinositol-3 kinase, but decreased the phosphorylation of Akt and mammalian target of rapamycin (mTOR), and down-regulated the expression of Raptor and p70 ribosomal kinase S6 kinase, suggesting that alcohol impaired protein synthesis signaling pathway in skeletal muscle of tumor-bearing mice. Alcohol consumption enhanced the expression of myostatin in skeletal muscle, plasma, and tumor, but did not affect the expression of myostatin in non-tumor-bearing mice. In TNFα knockout mice, the effects of alcohol-enhanced expression of myostatin and protein degradation-related signaling molecules, and decreased protein synthesis signaling in skeletal muscle were abolished. Consequently, alcohol consumption neither affected cancer-associated cachexia nor decreased the survival of TNFα KO mice bearing cachectic cancer. CONCLUSIONS: Chronic alcohol consumption enhances cancer-associated skeletal muscle loss through suppressing Akt/mTOR-mediated protein synthesis pathway and enhancing protein degradation pathways. This process is initiated by TNFα and mediated by myostatin.

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice.

Chronic alcohol consumption increases the susceptibility to infectious diseases by compromising immune system. Cytomegalovirus infection is common in human and usually is asymptomatic in immunocompetent people. However, it can induce life-threatening medical complications in immunocompromised individuals such as alcoholics. How chronic alcohol consumption exacerbates cytomegalovirus infection is not known. Herein, we used a mouse cytomegalovirus model to study the underlying cellular and molecular mechanism. We found that alcohol consumption increased viral titers in spleen after 4 days of infection, enhanced body weight loss and inhibited splenomegaly during the acute phase of infection. Blood level of IFN-ß, splenic IFN-γ and granzyme B-producing NK cells were lower in alcohol-consuming mice than in water-drinking mice at 12 h after viral infection. Moreover, alcohol consumption decreased IL-15-producing DC after 36 h infection, inhibited NK cell, specifically Ly49H+ NK cell maturation and proliferation 3-6 days after viral infection. Surprisingly, alcohol consumption enhanced NK cell and CD8+ T cell continuous activation and increased granzyme B-producing cells. However, alcohol consumption decreased the expression of perforin in spleen and liver. Taken together, chronic alcohol consumption exacerbates cytomegalovirus infection via impairing non-specific and specific NK cell activation, specifically IFN-γ and perforin production.

Optimal surgical intervention for achalasia: laparoscopic or robotic approach.

Laparoscopic esophageal myotomy is the standard surgical intervention for achalasia. Compared to standard laparoscopic techniques, use of the robot has theoretical advantages of improved visualization and dexterity. We evaluated the University of Arizona's experience with the two alternatives to compare outcomes. Patients who underwent either laparoscopic or robot-assisted myotomy were identified from a retrospective database from 1/1/2006 to 12/31/2015. Patient demographics, prior treatment, intra-operative complications, operative time, post-operative length of stay and complications, and long-term results were compared between the two groups. We identified 35 laparoscopic and 37 robot-assisted Heller myotomies performed by multiple surgeons. Patient demographics were similar between the two groups with no statistical difference in age, gender, previous operations, pre-operative Botox or dilation treatment, or pre-op Eckardt score. In univariate analysis, the patients with the robotic procedure received a longer myotomy (5.85 cm vs. 5.56 cm for esophageal and 2.92 cm vs. 2.68 cm for gastric) and had a lower post-operative Eckardt score (0.51 vs. 1.09). A trend toward lower incidence of recurrent achalasia symptoms was found in the robotic group (0 patient vs. 4 patients) compared with those who had laparoscopic surgery (p < 0.05). Multivariate analysis showed that a longer gastric myotomy was associated with a lower recurrence rate (p = 0.0002). Both laparoscopic and robot-assisted Heller myotomy can provide definitive treatment of achalasia with good results and few complications. The mechanical advantage provided by the robotic approach may improve outcomes by providing a more complete myotomy and durable long-term result.

Chronic alcohol consumption exacerbates murine cytomegalovirus infection via impairing nonspecific and specific NK activation in mice.

Chronic alcohol consumption increases the susceptibility to infectious diseases by compromising the immune system. Cytomegalovirus infection is common in humans and usually is asymptomatic in immunocompetent people. However, it can induce life-threatening medical complications in immunocompromised individuals such as alcoholics. How chronic alcohol consumption exacerbates cytomegalovirus infection is not known. Herein, we used a mouse cytomegalovirus model to study the underlying cellular and molecular mechanism. We found that alcohol consumption increased viral titers in spleen after 4 days of infection, enhanced body weight loss and inhibited splenomegaly during the acute phase of infection. Blood level of IFN-ß, splenic IFN-γ and granzyme B-producing NK cells were lower in alcohol-consuming mice than in water-drinking mice at 12 hours after viral infection. Moreover, alcohol consumption decreased IL-15-producing DC after 36 hours infection, inhibited NK cell, specifically Ly49H+ NK cell maturation and proliferation 3-6 days after viral infection. Surprisingly, alcohol consumption enhanced NK cell and CD8+ T-cell continuous activation and increased granzyme B-producing cells. However, alcohol consumption decreased the expression of perforin in spleen and liver. Taken together, chronic alcohol consumption exacerbates cytomegalovirus infection via impairing nonspecific and specific NK cell activation, specifically IFN-γ and perforin production.

Changes in Tracheostomy- and Intubation-Related Tracheal Stenosis: Implications for Surgery.

BACKGROUND: This study sought to identify the changing characteristic patterns and locations of stenosis after tracheostomy or intubation and to assess the risk factors associated with perioperative complication and restenosis after primary resection and reconstruction. METHODS: A retrospective review was performed (January /2012 to March 2015) on patients treated at the University of Arizona Medical Center (Tucson, Arizona) who had symptomatic tracheal stenosis secondary to prolonged intubation or tracheostomy. Data on demographics, surgical approach, and outcome were obtained. Analysis was performed using the χ2 test, Kaplan-Meier estimate of survival, Cox proportional hazards survival analysis, and univariate and multivariate logistic regression. RESULTS: Forty-eight patients were referred for surgical resection, and 36 patients underwent primary resection and reconstruction; 72% of patients had previous endobronchial treatments for stenosis. Fourteen patients had postintubation tracheal stenosis, and 22 had tracheostomy-related stenosis (16 percutaneous, 6 open tracheostomy). Among all patients, 52.8% had stenosis proximal to or involving the cricoid; 72.7% of patients with tracheostomy-related stenosis had stenosis at or proximal to the cricoid, whereas only 21.4% of the patients with intubation-related stenosis had a similar location. Nineteen patients underwent laryngotracheal resection, and 17 patients had tracheal resection. The mean length of resection was 3.6 cm. A body mass index greater than 35 was associated with increased perioperative complications (p = 0.012). In multivariate analysis, patients younger than 30 years of age at operation had an increased relative risk of recurrence. CONCLUSIONS: Recent advances in percutaneous tracheostomy have increased the numbers of patients presenting with proximal tracheal stenosis, thus necessitating more complex subglottic resection and reconstruction. The anastomotic and overall complication rate remains low despite these more complex operations.

Quality of routine health data collected by health workers using smartphone at primary health care in Ethiopia.

BACKGROUND: Mobile phone based applications are considered by many as potentially useful for addressing challenges and improving the quality of data collection in developing countries. Yet very little evidence is available supporting or refuting the potential and widely perceived benefits on the use of electronic forms on smartphones for routine patient data collection by health workers at primary health care facilities. METHODS: A facility based cross sectional study using a structured paper checklist was prepared to assess the completeness and accuracy of 408 electronic records completed and submitted to a central database server using electronic forms on smartphones by 25 health workers. The 408 electronic records were selected randomly out of a total of 1772 maternal health records submitted by the health workers to the central database over a period of six months. Descriptive frequencies and percentages of data completeness and error rates were calculated. RESULTS: When compared to paper records, the use of electronic forms significantly improved data completeness by 209 (8%) entries. Of a total 2622 entries checked for completeness, 2602 (99.2%) electronic record entries were complete, while 2393 (91.3%) paper record entries were complete. A very small percentage of error rates, which was easily identifiable, occurred in both electronic and paper forms although the error rate in the electronic records was more than double that of paper records (2.8% vs. 1.1%). More than half of entry errors in the electronic records related to entering a text value. CONCLUSIONS: With minimal training, supervision, and no incentives, health care workers were able to use electronic forms for patient assessment and routine data collection appropriately and accurately with a very small error rate. Minimising the number of questions requiring text responses in electronic forms would be helpful in minimizing data errors.

Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15.

NK cells are innate immune cells and have important roles in antiviral and antitumor immunity. Based on the transcriptional regulation, organ distribution, and cell function, NK cells have recently been further divided into cytotoxic conventional NK cells (cNK) and noncytotoxic helper-like group 1 innate lymphoid cells (ILC1s). It is well known that chronic alcohol consumption decreases peripheral NK cell number and cytolytic activity; however, the underlying mechanism remains to be elucidated. How chronic alcohol consumption affects ILC1s is, to our knowledge, completely unexplored. Herein, we used a well-established mouse model of chronic alcohol consumption to study the effects of alcohol on transcription factor expression, maturation, and cytokine production of cNK cells and ILC1s in various organs. We found that alcohol consumption significantly decreased Eomes-expressing cNK cells in all the examined organs, except BM, but did not significantly affect ILC1s. Alcohol consumption compromised cNK cell development and maturation. Exogenous IL-15/IL-15Rα treatment caused full recovery of Eomes-expressing cNK cell number and maturation. Taken together, our data indicated that chronic alcohol consumption decreases cNK cell number and cytolytic activity by arresting cNK cell development at the CD27+CD11b+ stage. This developmental arrest of NK cells results from a lack of IL-15 availability in the microenvironment. IL-15/IL-15Rα treatment can recover alcohol consumption-induced developmental defect in NK cells.

Changes in Thoracic Surgery Experience During General Surgery Residency: A Review of the Case Logs From the Accreditation Council for Graduate Medical Education.

BACKGROUND: Although exposure to thoracic surgery is mandated in general surgery residency, little is known about the mix of cases that residents use to meet this requirement and how this has changed over time. We report the experience of general thoracic surgery among general surgery residents using the Accreditation Council for Graduate Medical Education (ACGME) database. METHODS: We performed a retrospective review of the prospectively maintained ACGME resident case log database from 2003 to 2013. Thoracic cases were categorized by procedure type, year, and level of resident participation. A linear regression model was used to determine if there was a significant trend in case volumes over time. RESULTS: First assist volumes decreased in the 90th (-1.46 cases/year, p = 0.0012), 70th (-0.77 cases/year, p = 0.0005), 50th (-0.46 cases/year, p = 0.0013), and 30th percentiles (-0.16 cases/year, p = 0.0187). Pneumonectomy volumes decreased for surgeons junior (-0.01 cases/year, p = 0.0013) and chief residents (-0.01 cases/year, p = 0.005), as did open lobectomy (surgeon junior, -0.202 cases/year, p < 0.0001; chief, -0.08 cases/year, p ≤ 0.0013). Video-assisted (VATS) lobectomy increased for the surgeons junior (0.22 cases/year, p < 0.0001) and chief residents (0.045 cases/year, p < 0.0001). Surgeons junior also had increased volumes of VATS exploratory thoracoscopy (0.11 cases/year, p = 0.0003) and VATS pleurodeisis (0.13 cases/year, p < 0.0001). CONCLUSIONS: Whereas total thoracic volumes on the whole have not changed significantly, resident participation as a first assistant and in key thoracic cases has decreased over the last 11 years, while participation in VATS and minor cases has increased.

Thermal conditions experienced during differentiation affect metabolic and contractile phenotypes of mouse myotubes.

Central pathways regulate metabolic responses to cold in endotherms to maintain relatively stable internal core body temperatures. However, peripheral muscles routinely experience temperatures lower than core body temperature, so that it would be advantageous for peripheral tissues to respond to temperature changes independently from core body temperature regulation. Early developmental conditions can influence offspring phenotypes, and here we tested whether developing muscle can compensate locally for the effects of cold exposure independently from central regulation. Muscle myotubes originate from undifferentiated myoblasts that are laid down during embryogenesis. We show that in a murine myoblast cell line (C2C12), cold exposure (32°C) increased myoblast metabolic flux compared with 37°C control conditions. Importantly, myotubes that differentiated at 32°C compensated for the thermodynamic effects of low temperature by increasing metabolic rates, ATP production, and glycolytic flux. Myotube responses were also modulated by the temperatures experienced by "parent" myoblasts. Myotubes that differentiated under cold exposure increased activity of the AMP-stimulated protein kinase (AMPK), which may mediate metabolic changes in response cold exposure. Moreover, cold exposure shifted myosin heavy chains from slow to fast, presumably to overcome slower contractile speeds resulting from low temperatures. Adjusting thermal sensitivities locally in peripheral tissues complements central thermoregulation and permits animals to maintain function in cold environments. Muscle also plays a major metabolic role in adults, so that developmental responses to cold are likely to influence energy expenditure later in life.

Factors in the Selection and Management of Chest Tubes After Pulmonary Lobectomy: Results of a National Survey of Thoracic Surgeons.

BACKGROUND: This study determined patterns of chest tube (CT) selection and management after open lobectomy and minimally invasive lobectomy by thoracic surgeons. METHODS: Surveys were sent electronically to 5,175 thoracic surgeons, and 475 were completed. Responses, blinded so individuals could not be identified, were analyzed and compared according to surgeon characteristics (academic/private practice, years in practice, lobectomy volume, and geographic region). All indicated differences were statistically significant (p < 0.05 by χ(2) tests). RESULTS: CT selection: Most surgeons prefer rigid tubes, and the size most commonly used was 28F. Most place 2 CTs after open lobectomy and 1 CT after minimally invasive lobectomy. Academic surgeons are more likely than private surgeons to use 1 tube after open lobectomy, but both prefer 1 tube after minimally invasive lobectomy. Younger surgeons and high-volume surgeons are more likely to use 1 CT than senior surgeons and low-volume surgeons after both open lobectomy and minimally invasive lobectomy. CT management: Academic and younger surgeons remove the CT sooner after open lobectomy. Younger and high-volume surgeons remove the CT with greater drainage amounts. All groups remove CTs sooner after minimally invasive lobectomy than after open lobectomy. Approximately half of surgeons get a daily chest roentgenogram. Younger and low-volume surgeons are most likely to discharge patients with Heimlich valves, although overall use was in less than 5% (49 of 475) of respondents. Most surgeons believe clinical experience rather than training or the literature determined their CT strategy. CONCLUSIONS: This survey determined the difference in CT management among various groups of surgeons. Clinical experience was the most important factor in determining their CT strategy.

Health workers' experiences, barriers, preferences and motivating factors in using mHealth forms in Ethiopia.

BACKGROUND: Mobile health (mHealth) applications, such as innovative electronic forms on smartphones, could potentially improve the performance of health care workers and health systems in developing countries. However, contextual evidence on health workers' barriers and motivating factors that may influence large-scale implementation of such interfaces for health care delivery is scarce. METHODS: A pretested semistructured questionnaire was used to assess health workers' experiences, barriers, preferences, and motivating factors in using mobile health forms on smartphones in the context of maternal health care in Ethiopia. Twenty-five health extension workers (HEWs) and midwives, working in 13 primary health care facilities in Tigray region, Ethiopia, participated in this study. RESULTS: Over a 6-month period, a total of 2,893 electronic health records of 1,122 women were submitted to a central computer through the Internet. Sixteen (69.6%) workers believed the forms were good reminders on what to do and what questions needed to be asked. Twelve (52.2%) workers said electronic forms were comprehensive and 9 (39.1%) workers saw electronic forms as learning tools. All workers preferred unrestricted use of the smartphones and believed it helped them adapt to the smartphones and electronic forms for work purposes. With regards to language preference, 18 (78.3%) preferred using the local language (Tigrinya) version of the forms to English. Indentified barriers for not using electronic forms consistently include challenges related to electronic forms (for example, problem with username and password setting as reported by 5 (21.7%), smartphones (for example, smartphone froze or locked up as reported by 9 (39.1%) and health system (for example, frequent movement of health workers as reported by 19 (82.6%)). CONCLUSIONS: Both HEWs and midwives found the electronic forms on smartphones useful for their day-to-day maternal health care services delivery. However, sustainable use and implementation of such work tools at scale would be daunting without providing technical support to health workers, securing mobile network airtime and improving key functions of the larger health system.

Mobile health data collection at primary health care in Ethiopia: a feasible challenge.

OBJECTIVES: Feasibility assessment of mobile health (mHealth) data collection at primary health care in Ethiopia. STUDY DESIGN AND SETTING: A total of 14 health workers were recruited from 12 primary health care facilities to use smartphones, installed with customized data collection application and electronic maternal health care forms for assessing pregnant women's health for 6 months. Qualitative approaches comprising in-depth interviews and field notes were used to document the users' perception and experience in using the application and forms. RESULTS: All health workers had never had previous exposure to smartphones and electronic forms, but they got used to them easily. Over 6 months, all health workers completed a total of 952 patient records using the forms on smartphones. Health workers' acceptability and demand for the application and forms were high. In introducing the application, nontechnical challenges were more difficult to solve than technical challenges. CONCLUSION: Introducing an mHealth application at primary health care for routine collection of health data relevant to maternal health at a small scale was feasible. Nonetheless, implementing a system of assigning unique and consistent patient identifier, standardization of health services, and improving mobile network coverage would be prerequisites for scaled-up usage of such an application.

Meeting community health worker needs for maternal health care service delivery using appropriate mobile technologies in Ethiopia.

BACKGROUND: Mobile health applications are complex interventions that essentially require changes to the behavior of health care professionals who will use them and changes to systems or processes in delivery of care. Our aim has been to meet the technical needs of Health Extension Workers (HEWs) and midwives for maternal health using appropriate mobile technologies tools. METHODS: We have developed and evaluated a set of appropriate smartphone health applications using open source components, including a local language adapted data collection tool, health worker and manager user-friendly dashboard analytics and maternal-newborn protocols. This is an eighteen month follow-up of an ongoing observational research study in the northern of Ethiopia involving two districts, twenty HEWs, and twelve midwives. RESULTS: Most health workers rapidly learned how to use and became comfortable with the touch screen devices so only limited technical support was needed. Unrestricted use of smartphones generated a strong sense of ownership and empowerment among the health workers. Ownership of the phones was a strong motivator for the health workers, who recognised the value and usefulness of the devices, so took care to look after them. A low level of smartphones breakage (8.3%,3 from 36) and loss (2.7%) were reported. Each health worker made an average of 160 mins of voice calls and downloaded 27Mb of data per month, however, we found very low usage of short message service (less than 3 per month). CONCLUSIONS: Although it is too early to show a direct link between mobile technologies and health outcomes, mobile technologies allow health managers to more quickly and reliably have access to data which can help identify where there issues in the service delivery. Achieving a strong sense of ownership and empowerment among health workers is a prerequisite for a successful introduction of any mobile health program.

Safety-net burden hospitals and likelihood of curative-intent surgery for non-small cell lung cancer.

BACKGROUND: Black patients are less likely to undergo surgery for early-stage non-small cell lung cancer (NSCLC) compared with white patients, and are more likely to undergo resection at low-volume hospitals. However, little is known about the relationship between hospital safety-net burden and the likelihood of curative-intent surgery for black and white patients. This study analyzes whether hospital safety-net burden is associated with curative-intent surgery among adult early-stage NSCLC patients treated at facilities accredited by the American College of Surgeons Commission on Cancer. STUDY DESIGN: Adult patients diagnosed with invasive initial primary early-stage (TNM I-II) NSCLC during 2003-2005 were obtained from the National Cancer Data Base. Curative-intent surgery included anatomic resection, wedge resection, and segmentectomy. Hospital safety-net burden was defined as the percent of cancer patients per facility that were Medicaid-insured or uninsured. Generalized estimating equations and linear mixed models were used to control for clustering by facility. RESULTS: Of 52,853 evaluable patients, those treated at high safety-net burden facilities were significantly less likely (unadjusted p < 0.0001) to undergo curative-intent surgery than patients treated at low safety-net burden facilities. Controlling for patient and other facility characteristics, high safety-net burden remained significantly associated (p < 0.0001) with reduced likelihood of curative-intent surgery overall (odds ratio = 0.69; 95% CI, 0.62-0.77) and in black- and white-only models (odds ratio = 0.59, 95% CI, 0.48-0.73; odds ratio = 0.71; 95% CI, 0.63-0.80, respectively). CONCLUSIONS: Both black and white adult patients treated for early-stage NSCLC at high safety-net burden facilities are less likely to undergo curative-intent surgery than those treated at low safety-net burden facilities. Innovative solutions are needed to ensure quality cancer care at high safety-net burden facilities.

Characterization of the Interaction between hantavirus nucleocapsid protein (N) and ribosomal protein S19 (RPS19).

Hantaviruses, members of the Bunyaviridae family, are negative-stranded emerging RNA viruses and category A pathogens that cause serious illness when transmitted to humans through aerosolized excreta of infected rodent hosts. Hantaviruses have evolved a novel translation initiation mechanism, operated by nucleocapsid protein (N), which preferentially facilitates the translation of viral mRNAs. N binds to the ribosomal protein S19 (RPS19), a structural component of the 40 S ribosomal subunit. In addition, N also binds to both the viral mRNA 5' cap and a highly conserved triplet repeat sequence of the viral mRNA 5' UTR. The simultaneous binding of N at both the terminal cap and the 5' UTR favors ribosome loading on viral transcripts during translation initiation. We characterized the binding between N and RPS19 and demonstrate the role of the N-RPS19 interaction in N-mediated translation initiation mechanism. We show that N specifically binds to RPS19 with high affinity and a binding stoichiometry of 1:1. The N-RPS19 interaction is an enthalpy-driven process. RPS19 undergoes a conformational change after binding to N. Using T7 RNA polymerase, we synthesized the hantavirus S segment mRNA, which matches the transcript generated by the viral RNA-dependent RNA polymerase in cells. We show that the N-RPS19 interaction plays a critical role in the translation of this mRNA both in cells and rabbit reticulocyte lysates. Our results demonstrate that the N-mediated translation initiation mechanism, which lures the host translation machinery for the preferential translation of viral transcripts, primarily depends on the N-RPS19 interaction. We suggest that the N-RPS19 interaction is a novel target to shut down the N-mediated translation strategy and hence virus replication in cells.