Treatment Of Norovirus Infections Research Articles

Norovirus in Cancer Patients: A Review.

Norovirus (NoV) is the leading cause of viral-related diarrhea in cancer patients, in whom it can be chronic, contributing to decreased quality of life, interruption of cancer care, malnutrition, and altered mucosal barrier function. Immunosuppressed cancer patients shed NoV for longer periods of time than immunocompetent hosts, favoring quasispecies development and emergence of novel NoV variants. While nucleic acid amplification tests (NAATs) for NoV diagnosis have revolutionized our understanding of NoV burden of disease, not all NAATs provide information on viral load or infecting genotype. There is currently no effective antiviral or vaccine for chronic NoV infections. Screening for inhibitors of NoV replication in intestinal organoid culture models and creation of NoV-specific adoptive T cells are promising new strategies to develop treatments for chronic NoV in immunosuppressed patients. Herein we summarize data on the epidemiology, clinical manifestations, diagnostic challenges, and treatment of NoV infection in patients with cancer.

The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study.

Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes.IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.

Development of multi-epitope subunit vaccine for protection against the norovirus’ infections based on computational vaccinology

Human Norovirus belongs to a family Calciviridae, and was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as “winter vomiting disease.” Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study, capsid protein (A7YK10), small protein (A7YK11), and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for the subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA, and rampage servers. The modelled vaccine was docked with TLR-7. The stability of the docked complex was evaluated by MD simulation. To apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease. Communicated by Ramaswamy H. Sarma

S1623 Chronic Norovirus Gastroenteritis in a Patient With Common Variable Immunodeficiency Enteropathy: A Case Report

INTRODUCTION: Norovirus gastroenteritis is a self-limiting illness that is treated with supportive care. In immunocompromised patients, however, it is known to cause prolonged illness. Treatment remains controversial. We present a case of an immunocompromised patient with chronic norovirus gastroenteritis. CASE DESCRIPTION/METHODS: A 45–year-old Caucasian male presented to the emergency room with nausea, vomiting, loose stools up to 8/day, and 15-pound weight loss. He had a past medical history of common variable immune deficiency (CVID) with CVID associated enteropathy, vitiligo, history of extra-nodal marginal B-cell lymphoma, and celiac disease. Five months prior, he had a CVID enteropathy flare up and was prescribed oral steroids. Post steroids, he developed acute organizing pneumonia and was hospitalized. He had diarrhea which was treated with supportive care. Stool studies were positive for Norovirus 2. On admission, he was hemodynamically stable, and physical examination was remarkable for hypopigmented patches secondary to vitiligo. Abdomen had positive bowel sounds and was soft, non-tender, and non-distended. Laboratory workup was as shown in Table 1. Stool studies were positive for fecal lactoferrin and Norovirus 2. The rest of the infectious workup was negative. The patient was diagnosed with CVID enteropathy flare and was started on intravenous methylprednisolone 20 mg three times a day. He had mild improvement in his symptoms. Colonoscopy was performed and was grossly unremarkable. Random colon biopsies revealed active cryptitis but did not show a paucity of plasma cells or intraepithelial lymphocytosis, as shown in Figure 1. There were no histological signs of inflammatory bowel disease and staining for cytomegalovirus infection was negative. The patient was discharged on prednisone 40 mg once a day and nitazoxanide 500 mg for 14 days. Steroids helped only minimally, but after starting nitazoxanide, he had significant improvements in his symptoms and the frequency of his bowel movements decreased to 2-3 per day. At six months, he has been doing well with no reported adverse effects. DISCUSSION: This case demonstrates that immunocompromised patients with gastrointestinal manifestations can have prolonged norovirus infection, which might cause flare-ups of underlying gastrointestinal conditions. Hence, treatment of norovirus infection in such patients should be considered, with nitazoxanide a potentially effective treatment.Table 1.: Serum Laboratory Results.Figure 1.: Hematoxylin and eosin stain of a random colon biopsy revealing active neutrophilic infiltration of the crypts with no significant architectural abnormality.

Norovirus in Transplantation.

Noroviruses are among the most common cause of diarrhea in transplant recipients. The clinical spectrum of norovirus infection after transplant is increasingly being recognized. As substantial morbidity is now associated with norovirus infections in this population; the quest for rapid diagnostic modalities and newer therapies has expanded. Transplant recipients with norovirus infection are at risk for several complications, including protracted illness with malnutrition, organ failure, and chronic viral shedding. This review summarizes the current knowledge on the epidemiology, complications, diagnosis, and treatment of norovirus infection in the transplant setting.

Blood group substances as potential therapeutic agents for the prevention and treatment of infection with noroviruses proving novel binding patterns in human tissues.

Blood group-related glycans determining ABO and Lewis blood groups are known to function as attachment factors for most of the norovirus (NoV) strains. To identify binding specificity of each NoV, recombinant norovirus-like particles (VLPs) and human saliva samples with different ABO, Lewis phenotypes and secretor status have been commonly applied. When binding specificities of VLPs prepared from 16 different genotypes of NoVs in GI and GII genogroups were characterized in samples of human gastric mucosa compared to human saliva based on blood group phenotypes, considerable differences were observed for several strains. Novel binding specificities determined by an ELISA using preparations from human gastric mucosa were also ascertained by immunohistochemical analyses using human jejunal mucosa, widely believed to be susceptible to NoV infection. Further, A, B and O(H) blood group substances prepared from porcine and squid tissues were found to be effective for preventing ABO blood group-specific binding of VLPs to both saliva and mucosa samples. Therefore, these blood group substances might have potential for the prevention and treatment of NoV infection.

Progress Towards the Prevention and Treatment of Norovirus Infections

Noroviruses are now recognized as the major cause of acute gastroenteritis in the developed world, yet our ability to prevent and control infection is limited. Recent work has highlighted that, while typically an acute infection in the population, immunocompromised patients often experience long-term infections that may last many years. This cohort of patients and those regularly exposed to infectious material, for example, care workers and others, would benefit greatly from the development of a vaccine or antiviral therapy. While a licensed vaccine or antiviral has yet to be developed, work over the past 10 years in this area has intensified and trials with a vaccine candidate have proven promising. Numerous antiviral targets and small molecule inhibitors that have efficacy in cell culture have now been identified; however, further studies in this area are required in order to make these suitable for clinical use.