Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population

Currier, Rebecca L.; Payne, Daniel C.; Staat, Mary Allen; Selvarangan, Rangaraj; Shirley, S. Hannah; Halasa, Natasha; Boom, Julie A.; Englund, Janet A.; Szilâgyi, Peter G.; Harrison, Christopher J.; Klein, Eileen J.; Weinberg, Geoffrey A.; Wikswo, Mary E.; Parashar, Umesh D.; Vinjé, Jan; Morrow, Ardythe L.

doi:10.1093/cid/civ165

Cited by 103 publications

(99 citation statements)

References 35 publications

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“…Even at high doses of the virus, none of the individuals with defective FUT2 genes showed clinical signs of infection, developed a norovirus antibody response, or had detectable virus in stool samples, thus decisively demonstrating the role of FUT2 in controlling susceptibility to norovirus infection (88). The requirement for active FUT2 in norovirus infections has been confirmed by several subsequent studies on additional cohorts (31, 89, 93, 158). However, the protective effects of altered FUT2 alleles may be norovirus strain specific (46), and additional related factors, such as ABO blood type, also influence susceptibility (63, 96, 107).…”

Section: Norovirus and Rotavirusmentioning

confidence: 57%

Human Genetic Determinants of Viral Diseases

et al. 2017

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Much progress has been made in the identification of specific human gene variants that contribute to enhanced susceptibility or resistance to viral diseases. Herein we review multiple discoveries made with genome-wide or candidate gene approaches that have revealed significant insights into virus–host interactions. Genetic factors that have been identified include genes encoding virus receptors, receptor-modifying enzymes, and a wide variety of innate and adaptive immunity-related proteins. We discuss a range of pathogenic viruses, including influenza virus, respiratory syncytial virus, human immunodeficiency virus, human T cell leukemia virus, human papilloma virus, hepatitis B and C viruses, herpes simplex virus, norovirus, rotavirus, parvovirus, and Epstein-Barr virus. Understanding the genetic underpinnings that affect infectious disease outcomes should allow tailored treatment and prevention approaches in the future.

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Section: Norovirus and Rotavirusmentioning

confidence: 57%

Human Genetic Determinants of Viral Diseases

et al. 2017

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“…Interestingly, this is the approximate proportion (25-26%) of non-Hispanic US infants found in a control group to be FUT2 (a [1,2] fucosyltransferase 2) nonsecretors. 8,9 FUT2 nonsecretors may be protected against infection with P[8] rotavirus such as the vaccine virus contained in Rotarix Ò . 8,10-12 However, we did not perform serologic assessments to more fully determine which infants likely had "vaccine-take," and, as described earlier, the duration of shedding from just passive transit of vaccine virus is not known.…”

Section: ããmentioning

confidence: 99%

Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix®

Mijatovic-Rustempasic

Immergluck

Parker

et al. 2017

Human Vaccines & Immunotherapeutics

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Thirty-three infants aged »2 months had serial stool samples collected after receipt of Rotarix Ò vaccine dose 1, and were assessed for shedding of porcine circovirus type 1 DNA and Rotavirus group A RNA by molecular methods. We did not find strong evidence that porcine circovirus type 1 replication occurred. Porcine circovirus type 1 genome with the same sequence as that in Rotarix Ò was detected in a few infants as late as day 13; while this timing could suggest there may have been replication and not just transient passage through the gastrointestinal tract, the lack of increase in copy number in any infant supports transient passage and there are inherent limitations to the results. We found that 21% of infants did not shed Rotarix Ò RVA RNA beyond the day 3 sample, which may suggest lack of vaccine virus replication. Of the infants in whom Rotarix RVA RNA shedding continued, peak copy numbers were reached on days 3-5 for »40%, and after day 5 in »60%, and shedding can be prolonged ( 45 days).

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“…Another key player during NoV infection is fucosyltransferase 2 , or FUT2, whose protein expression is critical for susceptibility to most (but not all) HNoV strains [49,50]. FUT2 activity is required during the synthesis of ABO histo-blood group antigens (HBGAs), which are attachment factors or receptors that facilitate binding of some caliciviruses to cells [51,52].…”

Section: Nov Infection and Diseasementioning

confidence: 99%

Norovirus Regulation by Host and Microbe

Baldridge

Turula

Wobus

2016

Trends in Molecular Medicine

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Norovirus (NoV) infection is the leading cause of epidemic gastroenteritis globally, and can lead to detrimental chronic infection in immunocompromised hosts. Despite its prevalence as a cause of diarrheal illness, the study of human NoVs (HNoVs) has historically been limited by a paucity of models. The use of murine NoV (MNoV) to interrogate mechanisms of host control of viral infection has facilitated the exploration of different genetic mouse models, revealing roles for both innate and adaptive immunity in viral regulation. MNoV studies have also recently identified important interactions between the commensal micro-biota and NoV with clear extensions to HNoVs. In this review, we discuss the most current understanding of how the host, the microbiome, and their interactions regulate NoV infections.

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Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population

Abstract: FUT2 status is associated with norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding.

Cited by 103 publications

References 35 publications

Human Genetic Determinants of Viral Diseases

Human Genetic Determinants of Viral Diseases

Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix®

Norovirus Regulation by Host and Microbe

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