Cognitive processing speed in multiple sclerosis clinical practice: association with patient-reported outcomes, employment and magnetic resonance imaging metrics.

BACKGROUND AND PURPOSE: To analyze the relationship between cognitive processing speed, patient-reported outcome measures (PROMs), employment and magnetic resonance imaging (MRI) metrics in a large multiple sclerosis cohort. METHODS: Cross-sectional clinical data, PROMs, employment and MRI studies within 90 days of completion of the Processing Speed Test (PST), a technology-enabled adaptation of the Symbol Digit Modalities Test, were collected. MRI was analyzed using semi-automated methods. Correlations of PST score with PROMs and MRI metrics were examined using Spearman's rho. Wilcoxon rank sum testing compared MRI metrics across PST score quartiles and linear regression models identified predictors of PST performance. Effects of employment and depression were also investigated. RESULTS: In 721 patients (mean age 47.6 ± 11.4 years), PST scores were significantly correlated with all MRI metrics, including cord atrophy and deep gray matter volumes. Linear regression demonstrated self-reported physical disability, cognitive function, fatigue and social domains (adjusted R2  = 0.44, P < 0.001) as the strongest clinical predictors of PST score, whereas that of MRI variables included T2 lesion volume, whole-brain fraction and cord atrophy (adjusted R2  = 0.42, P < 0.001). An inclusive model identified T2 lesion volume, whole-brain fraction, self-reported upper extremity function, cognition and social participation as the strongest predictors of PST score (adjusted R2  = 0.51, P < 0.001). There was significant effect modification by depression on the relationship between self-reported cognition and PST performance. Employment status was associated with PST scores independent of age and physical disability. CONCLUSION: The PST score correlates with PROMs, MRI measures of focal and diffuse brain injury, and employment. The PST score is a feasible and meaningful measure for routine multiple sclerosis care.

The efficacy of 'static' training interventions for improving indices of cardiorespiratory fitness in premenopausal females.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death worldwide. Many risk factors for CVD can be modified pharmacologically; however, uptake of medications is low, especially in asymptomatic people. Exercise is also effective at reducing CVD risk, but adoption is poor with time-commitment and cost cited as key reasons for this. Repeated remote ischaemic preconditioning (RIPC) and isometric handgrip (IHG) training are both inexpensive, time-efficient interventions which have shown some promise in reducing blood pressure (BP) and improving markers of cardiovascular health and fitness. However, few studies have investigated the effectiveness of these interventions in premenopausal women. METHOD: Thirty healthy females were recruited to twelve supervised sessions of either RIPC or IHG over 4 weeks, or acted as non-intervention controls (CON). BP measurements, flow-mediated dilatation (FMD) and cardiopulmonary exercise tests (CPET) were performed at baseline and after the intervention period. RESULTS: IHG and RIPC were both well-tolerated with 100% adherence to all sessions. A statistically significant reduction in both systolic (- 7.2 mmHg) and diastolic (- 6 mmHg) BP was demonstrated following IHG, with no change following RIPC. No statistically significant improvements were observed in FMD or CPET parameters in any group. CONCLUSIONS: IHG is an inexpensive and well-tolerated intervention which may improve BP; a key risk factor for CVD. Conversely, our single arm RIPC protocol, despite being similarly well-tolerated, did not elicit improvements in any cardiorespiratory parameters in our chosen population.

The Predictive Ability of Pre-Operative Magnetic Resonance Imaging to Detect Pathological Outcomes in Prostate Cancer

Aims Accurate preoperative knowledge of tumour stage is important in preoperative planning at radical prostatectomy (RP). The aim of this study was to assess the predictive ability of multiparametric MRI for detecting pathological outcomes. Methods A retrospective review was performed of all patients who underwent RP over a 4 year period. Results Preoperative MRI was reported as showing T3 or T4 disease in 26(17.9%) out of 145 patients undergoing RP. Of these, 10(6.9%) had ECE (extra-capsular extension) and 1(0.7%) had SVI (seminal vesicle invasion) on final histology. The sensitivity and specificity of MRI for detecting ECE were 27.3% and 87.6%, respectively. The sensitivity and specificity of MRI for detecting SVI were 11.1% and 97.8%, respectively. The positive predictive values for determining ECE and SVI were 45.5% and 25%, respectively and negative predictive values were 75.9% and 94.4%. Conclusion MRI has good specificity but poor and heterogeneous sensitivity for predicting T3 disease in RP specimen.

Prison prescribing practice: practitioners' perspectives on why prison is different.

The current prison population in England and Wales has multiple, complex healthcare needs, presenting unique challenges to those caring for prisoners. Prison numbers have increased dramatically in the last 10 years. There are now approximately 84,000 prisoners in England and Wales and 120,000 new episodes of imprisonment each year . The authors all contribute to prison healthcare. Below, we discuss a key issue arising from first-hand experience of prisoners' health and social care needs, the prescription of psycho-active drugs by primary and secondary care practitioners. This is a core medical task, but beset with difficulties. These difficulties are not necessarily encountered in other areas of prison healthcare. However, they do illustrate how providing healthcare to prisoners is complex, often lacking a research base and can have pitfalls that are not obvious to the outsider.

"For them and for me": a qualitative exploration of peer befrienders' experiences supporting people with aphasia in the SUPERB feasibility trial.

PURPOSE: Peer-befriending, where support is offered by someone with shared lived experience, is an intervention that may facilitate successful adjustment in people experiencing post-stroke aphasia. This paper explores the experiences of the peer-befrienders. MATERIALS AND METHODS: People with aphasia were recruited as peer-befrienders within the SUPERB trial investigating befriending for people with post-stroke aphasia. The intervention comprised six visits over three months. Peer-befrienders were matched with at least one befriendee and received training and ongoing supervision. They were invited to participate in in-depth interviews which were analysed using framework analysis. RESULTS: All 10 befrienders participated in interviews, reporting on 19 matches. Seven main themes emerged: content of the sessions; befriender-befriendee relationship; negotiating the visits; handling boundaries and endings; positive impact of the befriending for befrienders and befriendees; and beliefs about the nature and value of peer support. While befrienders described challenges, such as negotiating journeys and witnessing distress, the role was perceived as a "secure challenge" due to the support and training received. CONCLUSIONS: Befrienders perceived the role as enjoyable and rewarding, and felt they were making a positive difference. They were unanimous in believing that people with aphasia can offer unique and valuable support to others with aphasia. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02947776, registered 28th October 2016.Implications for rehabilitationPeople with lived experience of stroke and aphasia were able to offer emotional and social peer support to others with aphasia within the SUPERB trial.Although there were challenges, peer befrienders perceived the role as rewarding and satisfying.Peer befrienders valued the training and ongoing supervision and support they received to deliver the intervention.It is recommended that rehabilitation professionals considering offering peer-befriending schemes provide training and ongoing supervision to support peer-befrienders fulfil their role, as well as practical support with, e.g., arranging visits.

"Loneliness can also kill:" a qualitative exploration of outcomes and experiences of the SUPERB peer-befriending scheme for people with aphasia and their significant others.

PURPOSE: People with aphasia post-stroke are at risk for depression and social isolation. Peer-befriending from someone with similar experiences may promote wellbeing and provide support. This paper explored the views of people with aphasia and their significant others about peer-befriending. MATERIALS AND METHODS: We conducted a qualitative study within a feasibility trial (SUPERB) on peer-befriending for people with post-stroke aphasia and low levels of distress. Of the 28 participants randomised to the intervention, semi-structured in-depth interviews were conducted with 10 purposively selected people with aphasia (at both 4- and 10-months post-randomisation) and five of their significant others (at 4-months). Interviews were analysed using Framework Analysis. RESULTS: Participants and their significant others were positive about peer-befriending and identified factors which influenced their experience: the befrienders' personal experience of stroke and aphasia, their character traits and the resulting rapport these created, the conversation topics they discussed and settings they met in, and the logistics of befriending, including planning visits and negotiating their end. Interviewees also made evaluative comments about the befriending scheme. CONCLUSION: Peer-befriending was an acceptable intervention. Benefits for emotional wellbeing and companionship were reported. The shared experience in the befriending relationship was highly valued.Implications for RehabilitationThe lived experience of stroke and aphasia of befrienders was highly valued by people with aphasia receiving peer-befriending.Training, regular supervision, and support for befrienders with practicalities such as organising visits ensured the befriending scheme was perceived as straightforward and acceptable by befriendees.Those receiving peer-befriending would recommend it to others; they found it beneficial, especially in terms of emotional wellbeing and companionship.

Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in healthy consumers.

Red meat from grass-fed animals, compared with concentrate-fed animals, contains increased concentrations of long-chain (LC) n-3 PUFA. However, the effects of red meat consumption from grass-fed animals on consumer blood concentrations of LC n-3 PUFA are unknown. The aim of the present study was to compare the effects on plasma and platelet LC n-3 PUFA status of consuming red meat produced from either grass-fed animals or concentrate-fed animals. A randomised, double-blinded, dietary intervention study was carried out for 4 weeks on healthy subjects who replaced their habitual red meat intake with three portions per week of red meat (beef and lamb) from animals offered a finishing diet of either grass or concentrate (n 20 consumers). Plasma and platelet fatty acid composition, dietary intake, blood pressure, and serum lipids and lipoproteins were analysed at baseline and post-intervention. Dietary intakes of total n-3 PUFA, as well as plasma and platelet concentrations of LC n-3 PUFA, were significantly higher in those subjects who consumed red meat from grass-fed animals compared with those who consumed red meat from concentrate-fed animals (P < 0·05). No significant differences in concentrations of serum cholesterol, TAG or blood pressure were observed between groups. Consuming red meat from grass-fed animals compared with concentrate-fed animals as part of the habitual diet can significantly increase consumer plasma and platelet LC n-3 PUFA status. As a result, red meat from grass-fed animals may contribute to dietary intakes of LC n-3 PUFA in populations where red meat is habitually consumed.

Identification of viral molecules recognized by influenza-specific human cytotoxic T lymphocytes.

Human cytotoxic T cells specific for influenza A virus were tested for recognition of each of the ten influenza A virus proteins expressed in target cells using recombinant vaccinia viruses. They recognized the matrix M1, polymerase PB2, and nucleoproteins of influenza virus in association with MHC class I antigens. These internal viral proteins were seen by CTL in conjunction with one or more of the available dependent HLA gene products. There was no detectable recognition of influenza virus surface glycoproteins in target cells.

An immunodominant class I-restricted cytotoxic T lymphocyte determinant of human immunodeficiency virus type 1 induces CD4 class II-restricted help for itself.

We have observed that a peptide corresponding to an immunodominant epitope of the HIV-1 envelope protein recognized by class I MHC-restricted CD8+ CTL can also induce T cell help for itself. The help is necessary for restimulation of CTL precursors in vitro with peptide alone in the absence of exogenous lymphokines, can be removed by depletion of CD4+ T cells, and can be replaced by exogenous IL-2. Whereas the CTL in BALB/c or B10. D2 mice are restricted by the class I molecule Dd, the Th cells are restricted by the class II molecule Ad, and the help can be blocked by anti-Ad mAb. To examine the genetic regulation of the induction of help, we studied B10.A mice that share the class I Dd molecule, but have different class II molecules, Ak and Ek. Spleen cells of immune B10.A mice behave like CD4-depleted BALB/c spleen cells in that they cannot be restimulated in vitro by the peptide alone, but can with peptide plus IL-2. Therefore, in the absence of exogenous lymphokines, peptide-specific help is necessary for restimulation with this immunodominant CTL epitope peptide, and in H-2d mice, this peptide stimulates help for itself as well as CTL. We speculate on the implications of these findings for the immunodominance of this peptide in H-2d mice, and for the selective advantage of pairing certain class I and class II molecules in an MHC haplotype.

Recognition of cloned vesicular stomatitis virus internal and external gene products by cytotoxic T lymphocytes.

It has generally been assumed that most if not all CTL specific for vesicular stomatitis virus (VSV)-infected cells recognize the viral glycoprotein (G), an integral membrane protein abundantly expressed on infected cell surfaces. Using recombinant vaccinia viruses containing copies of cloned VSV genes to examine CTL recognition of VSV, we have confirmed that G is recognized by VSV-specific CTL. More interestingly, however, we have also found that nucleocapsid protein (N), an internal virion protein, can be detected on infected cell surfaces using mAb, and serves as a major target antigen for VSV-specific CTL. In contrast to the highly serotype-specific recognition of G, N is recognized by a major population of CTL able to lyse cells infected with either the Indiana or New Jersey VSV serotypes. Using target cells expressing a cloned MHC class I gene, we could directly show that CTL recognition of N occurs in the context of the MHC Ld molecule.

The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis.

Cytotoxic T lymphocytes (CTL) are thought to contribute to viral clearance and liver cell injury during hepatitis B virus (HBV) infection. Using a strategy involving the in vitro stimulation of peripheral blood mononuclear cells (PBMC) with HBV-derived synthetic peptides containing HLA-A2.1, -A31, and -Aw68 binding motifs, we have previously described CTL responses to several epitopes within the HBV nucleocapsid and envelope antigens in patients with acute hepatitis. In this study we define six HLA-A2-restricted CTL epitopes located in the highly conserved reverse transcriptase and RNase H domains of the viral polymerase protein, and we show that the CTL response to polymerase is polyclonal, multispecific, and mediated by CD8+ T cells in patients with acute viral hepatitis, but that it is not detectable in patients with chronic HBV infection or uninfected healthy blood donors. Importantly, the peptide-activated CTL recognize target cells that express endogenously synthesized polymerase protein, suggesting that these peptides represent naturally processed viral epitopes. DNA sequence analysis of the viruses in patients who did not respond to peptide stimulation indicated that CTL nonresponsiveness was not due to infection by viral variants that differed in sequences from the synthetic peptides. CTL specific for one of the epitopes were unable to recognize several naturally occurring viral variants, except at high peptide concentration, underlining the HBV subtype specificity of this response. Furthermore, CTL responses against polymerase, core, and envelope epitopes were detectable for more than a year after complete clinical recovery and seroconversion, reflecting either the persistence of trace amounts of virus or the presence of long lived memory CTL in the absence of viral antigen. Finally, we demonstrated that wild type viral DNA and RNA can persist indefinitely, in trace quantities, in the serum and PBMC after complete clinical and serological recovery, despite a concomitant, vigorous, and sustained polyclonal CTL response. Since viral persistence is not due to escape from CTL recognition under these conditions, the data suggest that HBV may retreat into immunologically privileged sites from which it can seed the circulation and reach CTL-inaccessible tissues, thereby maintaining the CTL response in apparently cured individuals and, perhaps, prolonging the liver disease in patients with chronic hepatitis.

Anchor sequence-dependent endogenous processing of human immunodeficiency virus 1 envelope glycoprotein gp160 for CD4+ T cell recognition.

Human CD4+ T cell clones and cell lines were shown to lyse recombinant vaccinia virus-infected cells that synthesize the HIV-1 envelope glycoprotein gp160. The processing of endogenously synthesized gp160 for recognition by CD4+ T cells required that the protein, after synthesis on the rough endoplasmic reticulum and during subsequent cellular transport, remain attached to the luminal/extracellular membrane face by a hydrophobic anchor sequence.

Structural requirements for class I MHC molecule-mediated antigen presentation and cytotoxic T cell recognition of an immunodominant determinant of the human immunodeficiency virus envelope protein.

In H-2d mice, the immunodominant determinant of the HIV-1-IIIB gp160 envelope glycoprotein recognized by CD8+ CTL is represented by a 15-residue synthetic peptide (315-329: RIQRGPGRAFVTIGK). This peptide is seen in association with the Dd class I MHC molecule expressed on H-2k L cell fibroblast targets. We explored the structural requirements for CTL recognition of this peptide at the levels of both the peptide molecule and the class I MHC molecule. Using several transfectants expressing recombinant Dd/Ld molecules, we found that presentation of this epitope required both the alpha 1 and alpha 2 domains of the Dd molecule, in contrast to certain instances of allorecognition for which alpha 1 of Dd was sufficient in association with alpha 2 of Ld. Because this peptide derives from a hypervariable segment of the HIV envelope, substituted peptides could be used to define not only the structures affecting interaction of peptide with class I MHC molecule and with the TCR, but also the structural basis for the effect of naturally occurring viral variation on CTL recognition. The CTL-LINE specific for this HIV-1-IIIB-derived sequence could not recognize the HIV-1-RF variant-derived sequence from exactly the same site (315-329:--HIGPGRVIYATGQ). Peptides with single amino acid substitutions from the HIV-1-IIIB sequence toward the HIV-1-RF sequence were made to test the effect of each residue significantly affected recognition, and only one, 324(F), was obligatory. Moreover, both 322(R) and 324(F) substituted peptides failed to inhibit the binding of the wild type peptide to the MHC molecule. Therefore, the amino-acids 322(R) and 324(F) seem to be involved in regulating peptide interaction with the Dd class I MHC molecule. In contrast, 325(V) appeared to affect interaction with the TCR. We suggest that sequence variations among known HIV-1 isolates that affect peptide binding to MHC such as those described here, if occurring during the course of infection of an individual, could result in failure of the MHC molecules of that individual to present the peptide. If the number of dominant HIV CTL epitopes is indeed very limited, such a blind spot could allow the virus to escape immune control, proliferate rapidly, and cause AIDS.

gp100/pmel 17 is a murine tumor rejection antigen: induction of "self"-reactive, tumoricidal T cells using high-affinity, altered peptide ligand.

Many tumor-associated antigens are nonmutated, poorly immunogenic tissue differentiation antigens. Their weak immunogenicity may be due to "self"-tolerance. To induce autoreactive T cells, we studied immune responses to gp100/pmel 17, an antigen naturally expressed by both normal melanocytes and melanoma cells. Although a recombinant vaccinia virus (rVV) encoding the mouse homologue of gp100 was nonimmunogenic, immunization of normal C57BL/6 mice with the rVV encoding the human gp100 elicited a specific CD8(+) T cell response. These lymphocytes were cross-reactive with mgp100 in vitro and treated established B16 melanoma upon adoptive transfer. To understand the mechanism of the greater immunogenicity of the human version of gp100, we characterized a 9-amino acid (AA) epitope, restricted by H-2Db, that was recognized by the T cells. The ability to induce specific T cells with human but not mouse gp100 resulted from differences within the major histocompatibility complex (MHC) class I-restricted epitope and not from differences elsewhere in the molecule, as was evidenced by experiments in which mice were immunized with rVV containing minigenes encoding these epitopes. Although the human (hgp10025-33) and mouse (mgp10025-33) epitopes were homologous, differences in the three NH2-terminal AAs resulted in a 2-log increase in the ability of the human peptide to stabilize "empty" Db on RMA-S cells and a 3-log increase in its ability to trigger interferon gamma release by T cells. Thus, the fortuitous existence of a peptide homologue with significantly greater avidity for MHC class I resulted in the generation of self-reactive T cells. High-affinity, altered peptide ligands might be useful in the rational design of recombinant and synthetic vaccines that target tissue differentiation antigens expressed by tumors.

Evaluating S100B as a serum biomarker for central neurosarcoidosis.

BACKGROUND: S100B is a calcium-binding protein found primarily in glial cells. In the setting of neuronal injury and disruption of the blood brain barrier, S100B can leak into the cerebrospinal fluid and systemic circulation. OBJECTIVES: To determine if serum S100B distinguishes patients with central neurosarcoidosis (NS) from patients with extra-neurologic sarcoidosis (ENS) and healthy controls, and if S100B levels correlate with MRI measures of disease burden. METHODS: Patients were enrolled from the Cleveland Clinic Sarcoidosis Center. Patients with traumatic brain injury, central nervous system (CNS) infections, CNS malignancy, neurodegenerative disorders, schizophrenia, bipolar disorder, or melanoma were excluded. S100B levels were compared between patients with NS, ENS, and healthy controls, and between NS patients with varying degrees of post-contrast enhancement on MRI. RESULTS: Median (interquartile range) S100B levels were 101 pg/mL (92, 136) for 11 NS patients, 89 pg/mL (73, 107) for 11 ENS patients, and 60 pg/mL (39, 74) for 26 healthy controls. There was a significant difference between NS and control groups (p = 0.01). The difference between NS and ENS groups did not rise to the level of statistical significance (p = 0.178). S100B levels were significantly different between NS patients with varying degrees of enhancement on MRI (p = 0.04). CONCLUSIONS: S100B deserves additional study as a biomarker for CNS injury in NS. It may be useful as a longitudinal measure of disease activity.

Assembly of vaccinia virus: role of the intermediate compartment between the endoplasmic reticulum and the Golgi stacks.

Vaccinia virus, the prototype of the Poxviridae, is a large DNA virus which replicates in the cytoplasm of the host cell. The assembly pathway of vaccinia virus displays several unique features, such as the production of two structurally distinct, infectious forms. One of these, termed intracellular naked virus (INV), remains cells associated while the other, termed extracellular enveloped virus (EEV), is released from the cell. In addition, it has long been believed that INVs acquire their lipid envelopes by a unique example of de novo membrane biogenesis. To examine the structure and assembly of vaccinia virus we have used immunoelectron microscopy using antibodies to proteins of different subcellular compartments as well as a phospholipid analysis of purified INV and EEV. Our data are not consistent with the de novo model of viral membrane synthesis but rather argue that the vaccinia virus DNA becomes enwrapped by a membrane cisterna derived from the intermediate compartment between the ER and the Golgi stacks, thus acquiring two membranes in one step. Phospholipid analysis of purified INV supports its derivation from an early biosynthetic compartment. This unique assembly process is repeated once more when the INV becomes enwrapped by an additional membrane cisterna, in agreement with earlier reports. The available data suggest that after fusion between the outer envelope and the plasma membrane, mature EEV is released from the cell.

Vaccinia virus: a tool for research and vaccine development.

Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy.

Vaccinia virus recombinants: expression of VSV genes and protective immunization of mice and cattle.

Vesicular stomatitis virus (VSV) causes a contagious disease of horses, cattle, and pigs. When DNA copies of messenger RNA's for the G or N proteins of VSV were linked to a vaccinia virus promoter and inserted into the vaccinia genome, the recombinants retained infectivity and synthesized VSV polypeptides. After intradermal vaccination with live recombinant virus expressing the G protein, mice produced VSV-neutralizing antibodies and were protected against lethal encephalitis upon intravenous challenge with VSV. In cattle, the degree of protection against intradermalingually injected VSV was correlated with the level of neutralizing antibody produced following vaccination.

T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant.

The current prevalence of the acquired immune deficiency syndrome in humans has provoked renewed interest in methods of protective immunization against retrovirus-induced diseases. In this study, a vaccinia-retrovirus recombinant vector was constructed to study mechanisms of immune protection against Friend virus leukemia in mice. The envelope (env) gene from Friend murine leukemia virus (F-MuLV) was inserted into the genome of a vaccinia virus expression vector. Infected cells synthesized gp85, the glycosylated primary product of the env gene. Processing to gp70 and p15E, and cell surface localization, were similar to that occurring in cells infected with F-MuLV. Mice inoculated with live recombinant vaccinia virus had an envelope-specific T-cell proliferative response and, after challenge with Friend virus complex, developed neutralizing antibody and cytotoxic T cells (CTL) and were protected against leukemia. In contrast, unimmunized and control groups developed a delayed neutralizing antibody response, but no detectable CTL, and succumbed to leukemia. Genes of the major histocompatibility complex influenced protection induced by the vaccinia recombinant but not that induced by attenuated N-tropic Friend virus.

Ultraviolet-induced cell death blocked by a selenoprotein from a human dermatotropic poxvirus.

Selenium, an essential trace element, is a component of prokaryotic and eukaryotic antioxidant proteins. A candidate selenoprotein homologous to glutathione peroxidase was deduced from the sequence of molluscum contagiosum, a poxvirus that causes persistent skin neoplasms in children and acquired immunodeficiency syndrome (AIDS) patients. Selenium was incorporated into this protein during biosynthesis, and a characteristic stem-loop structure near the end of the messenger RNA was required for alternative selenocysteine decoding of a potential UGA stop codon within the open reading frame. The selenoprotein protected human keratinocytes against cytotoxic effects of ultraviolet irradiation and hydrogen peroxide, providing a mechanism for a virus to defend itself against environmental stress.