Deletion Mutants of VPg Reveal New Cytopathology Determinants in a Picornavirus

BACKGROUND: Success of a viral infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, viral replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes 3 copies of VPg. Why FMDV encodes three VPgs is unknown. METHODOLOGY AND PRINCIPAL FINDINGS: we have constructed four mutant FMDVS that encode only one VPG: either VPg(1), VPg(3), or two chimeric versions containing part of VPg(1) and VPg(3). All mutants, except that encoding only VPg(1), were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The effect of R55W in 2C was to mediate an increase in the extracellular viral RNA release without a detectable increase of total viral RNA that correlated with an enhanced capacity to alter and detach BHK-21 cells from the monolayer, the first stage of cell killing. CONCLUSIONS: The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. Implications for picornaviruses pathogenesis are discussed

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Aromatum, et simplicium aliquot medicamentorum apud Indos nascentium historia: primum quidem Lusitanica lingua per dialogos conscripta, a D.Garcia ab Horto, proregis Indiae medico: deinde Latino sermone in epitomen contracta, & iconibus ad viuum expressis, locupletioribusque annotatiunculis illustrata a Carolo Clusio Atrebate

La legatura è in pergamena rigida impressa a secco, il titolo manoscritto sul dorso. I tagli risultano essere spruzzati; presenti segnalini sul taglio. Sul dorso e sul piatto anteriore sono riportate manoscritte le collocazioni precedenti. Nel catalogo Marsili è riportato come: cum iconibus ad vivum depictis. Cat. Bonato. Restaurato nel 2009. Legato con: Florum, et coronariarum odoratarumque nonnullarum herbarum hi storia... (1569)

Aromatum, et simplicium aliquot medicamentorum apud Indos nascentium historia: primum quidem Lusitanica lingua per dialogos conscripta, a D.Garcia ab Horto, proregis Indiae medico: deinde Latino sermone in epitomen contracta, & iconibus ad viuum expressis, locupletioribusque annotatiunculis illustrata a Carolo Clusio Atrebate

La legatura è in pergamena rigida impressa a secco, il titolo manoscritto sul dorso. I tagli risultano essere spruzzati; presenti segnalini sul taglio. Sul dorso e sul piatto anteriore sono riportate manoscritte le collocazioni precedenti. Nel catalogo Marsili è riportato come: cum iconibus ad vivum depictis. Cat. Bonato. Restaurato nel 2009. Legato con: Florum, et coronariarum odoratarumque nonnullarum herbarum hi storia... (1569)

Aromatum, et simplicium aliquot medicamentorum apud Indos nascentium historia: primum quidem Lusitanica lingua per dialogos conscripta, a D.Garcia ab Horto, proregis Indiae medico: deinde Latino sermone in epitomen contracta, & iconibus ad viuum expressis, locupletioribusque annotatiunculis illustrata a Carolo Clusio Atrebate

La legatura è in pergamena rigida impressa a secco, il titolo manoscritto sul dorso. I tagli risultano essere spruzzati; presenti segnalini sul taglio. Sul dorso e sul piatto anteriore sono riportate manoscritte le collocazioni precedenti. Nel catalogo Marsili è riportato come: cum iconibus ad vivum depictis. Cat. Bonato. Restaurato nel 2009. Legato con: Florum, et coronariarum odoratarumque nonnullarum herbarum hi storia... (1569)

Aromatum, et simplicium aliquot medicamentorum apud Indos nascentium historia: primum quidem Lusitanica lingua per dialogos conscripta, a D.Garcia ab Horto, proregis Indiae medico: deinde Latino sermone in epitomen contracta, & iconibus ad viuum expressis, locupletioribusque annotatiunculis illustrata a Carolo Clusio Atrebate

La legatura è in pergamena rigida impressa a secco, il titolo manoscritto sul dorso. I tagli risultano essere spruzzati; presenti segnalini sul taglio. Sul dorso e sul piatto anteriore sono riportate manoscritte le collocazioni precedenti. Nel catalogo Marsili è riportato come: cum iconibus ad vivum depictis. Cat. Bonato. Restaurato nel 2009. Legato con: Florum, et coronariarum odoratarumque nonnullarum herbarum hi storia... (1569)

Aromatum, et simplicium aliquot medicamentorum apud Indos nascentium historia: primum quidem Lusitanica lingua per dialogos conscripta, a D.Garcia ab Horto, proregis Indiae medico: deinde Latino sermone in epitomen contracta, & iconibus ad viuum expressis, locupletioribusque annotatiunculis illustrata a Carolo Clusio Atrebate

La legatura è in pergamena rigida impressa a secco, il titolo manoscritto sul dorso. I tagli risultano essere spruzzati; presenti segnalini sul taglio. Sul dorso e sul piatto anteriore sono riportate manoscritte le collocazioni precedenti. Nel catalogo Marsili è riportato come: cum iconibus ad vivum depictis. Cat. Bonato. Restaurato nel 2009. Legato con: Florum, et coronariarum odoratarumque nonnullarum herbarum hi storia... (1569)

Aromatum, et simplicium aliquot medicamentorum apud Indos nascentium historia: primum quidem Lusitanica lingua per dialogos conscripta, a D.Garcia ab Horto, proregis Indiae medico: deinde Latino sermone in epitomen contracta, & iconibus ad viuum expressis, locupletioribusque annotatiunculis illustrata a Carolo Clusio Atrebate

La legatura è in pergamena rigida impressa a secco, il titolo manoscritto sul dorso. I tagli risultano essere spruzzati; presenti segnalini sul taglio. Sul dorso e sul piatto anteriore sono riportate manoscritte le collocazioni precedenti. Nel catalogo Marsili è riportato come: cum iconibus ad vivum depictis. Cat. Bonato. Restaurato nel 2009. Legato con: Florum, et coronariarum odoratarumque nonnullarum herbarum hi storia... (1569)