UC Santa Cruz UC Santa Cruz Previously Published Works Title Human Astrovirus 1-8 Seroprevalence Evaluation in a United States Adult Population. Permalink https://escholarship.org/uc/item/9nz336gs Journal Viruses, 13(6) ISSN 1999-4915 Authors Meyer, Lena Delgado-Cunningham, Kevin Lorig-Roach, Nicholas et al. Publication Date 2021-05-25 DOI 10.3390/v13060979 Peer reviewed eScholarship.org Powered by the California Digital Library University of California viruses Article Human Astrovirus 1–8 Seroprevalence Evaluation in a United States Adult Population Lena Meyer , Kevin Delgado-Cunningham, Nicholas Lorig-Roach, Jordan Ford and Rebecca M. DuBois * Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA; [email protected] (L.M.); [email protected] (K.D.-C.); [email protected] (N.L.-R.); [email protected] (J.F.) * Correspondence: [email protected] Abstract: Human astroviruses are an important cause of viral gastroenteritis globally, yet few studies have investigated the serostatus of adults to establish rates of previous infection. Here, we applied biolayer interferometry immunosorbent assay (BLI-ISA), a recently developed serosurveillance technique, to measure the presence of blood plasma IgG antibodies directed towards the human astrovirus capsid spikes from serotypes 1–8 in a cross-sectional sample of a United States adult population. The seroprevalence rates of IgG antibodies were 73% for human astrovirus serotype 1, 62% for serotype 3, 52% for serotype 4, 29% for serotype 5, 27% for serotype 8, 22% for serotype 2, 8% for serotype 6, and 8% for serotype 7. Notably, seroprevalence rates for capsid spike antigens correlate with neutralizing antibody rates determined previously. This work is the first seroprevalence study evaluating all eight classical human astrovirus serotypes. Citation: Meyer, L.; Delgado-Cunningham, K.; Keywords: human astrovirus; seroprevalence; biolayer interferometry immunosorbent assay Lorig-Roach, N.; Ford, J.; DuBois, R.M. Human Astrovirus 1–8 Seroprevalence Evaluation in a United States Adult Population. 1. Introduction Viruses 2021, 13, 979. https:// Astroviruses are a diverse family of small, nonenveloped, positive-sense RNA viruses doi.org/10.3390/v13060979 that infect mammalian and avian species [1]. Astrovirus infection is linked to a variety of disease manifestations, growth defects, and mortality in poultry [2]. In mammals, Academic Editors: astrovirus infection mainly causes viral gastroenteritis but can also be asymptomatic [3,4] Stacey Schultz-Cherry and or cause neurological syndromes and encephalitis in rare cases [5–8]. Human astroviruses Valerie Cortez are classified into three clades: classical serotypes 1–8, where serotype 1 is the most Received: 17 April 2021 prevalent globally [9–11], as well as the emerging serotypes MLB and VA [5,8]. Accepted: 24 May 2021 Human astroviruses (HAstVs) are a leading worldwide cause of viral gastroenteritis Published: 25 May 2021 but are among the most poorly characterized enteric viruses [12]. Young children, the elderly, and the immunocompromised are most threatened by astrovirus infection, espe- Publisher’s Note: MDPI stays neutral cially in developing countries [13–20]. Worldwide, human astrovirus infection accounts with regard to jurisdictional claims in for approximately 2 to 9% of all acute non-bacterial gastroenteritis in healthy children [21]. published maps and institutional affil- The United States sees an estimated 3.9 million cases of astrovirus gastroenteritis each iations. year [22]. However, immunofluorescence studies have demonstrated that about 75% of healthy adults have anti-astrovirus antibodies targeting at least one of the eight classi- cal serotypes [23], and another investigation showed that seroprevalence of neutralizing antibodies increases with age [10]. These findings suggest that cases of astrovirus gas- Copyright: © 2021 by the authors. troenteritis may be undercounted and that astrovirus disease may actually be a common Licensee MDPI, Basel, Switzerland. childhood infection. This article is an open access article Several lines of evidence highlight the importance of anti-astrovirus antibodies devel- distributed under the terms and oped in childhood in preventing reinfection in adulthood. Firstly, astrovirus infection is conditions of the Creative Commons rare in adults [23]. Although approximately 75% of adults have anti-astrovirus antibodies, Attribution (CC BY) license (https:// clinical investigations in healthy volunteers determined that more severe disease is associ- creativecommons.org/licenses/by/ ated with seronegativity for anti-astrovirus antibodies [24,25]. Finally, immunoglobulin 4.0/). Viruses 2021, 13, 979. https://doi.org/10.3390/v13060979 https://www.mdpi.com/journal/viruses VirusesViruses2021 2021, ,13 13,, 979 x FOR PEER REVIEW 22of of 1413 replacementglobulin replacement therapy resolved therapy a persistentresolved a human persistent astrovirus human infection astrovirus in an infection immunocom- in an promisedimmunocompromised patient [26]. Thesepatient studies [26]. These indicate studies that indicate a vaccine that and a vaccine therapeutic and therapeutic antibodies couldantibodies be developed could be todeveloped prevent and/orto prevent treat and/or human treat astrovirus human gastroenteritis.astrovirus gastroenteritis. PreviousPrevious structuralstructural studiesstudies have have defined defined the the structural structural domains domains of of the the human human astro- as- virustrovirus capsid capsid (Figure (Figure1A,B) 1A, [B)27 [27–30–].30 The]. The capsid capsid core core domain, domain, which which forms forms the the structural structural icosahedralicosahedral shell shell encapsulating encapsulating the the viral viral genome, genome, remains remains highly highly conserved conserved across across all eight all classicaleight classical serotypes, serotypes, ranging ranging from 83.3–97.0% from 83.3 sequence–97.0% sequence identity betweenidentity anybetween two serotypes any two (Tableserotypes1). In (Table contrast, 1). In the contrast, capsid spikethe capsid domain, spike which domain, forms which dimeric forms protrusions dimeric onprotru- the surfacesions on of the the surface viral particle, of the is viral quite particle, variable, is with quite a spreadvariable, of 41.4–75.7%with a spread sequence of 41. identity4–75.7% betweensequence any identity two serotypesbetween any (Table two2). serotypes Prior work (Table using 2). enzyme-linkedPrior work using immunosorbent enzyme-linked assaysimmunosorbent showed that assays both showed the core that and both spike the domains core and are spike antigenic domains [28]. are antigenic [28]. FigureFigure 1.1.The The humanhuman astrovirusastrovirus capsid.capsid. ((AA)) SchematicSchematic ofof thethe humanhuman astrovirusastrovirus capsidcapsid proteinprotein andand thethe recombinantrecombinant spikespike antigenantigen usedused inin thisthis study.study. ((BB)) TheThe maturemature humanhuman astrovirusastrovirus particle,particle, withwith thethe spikespike inin cyancyan andand thethe corecore inin darkdark blueblue (adapted(adapted from from [ 28[28]]).). Table 1. Sequence identity matrix across capsid core domains from human astrovirus serotypes 1– Table 1. Sequence identity matrix across capsid core domains from human astrovirus serotypes 1–8. 8. Core 11 Core2 2 Core 33 Core 44 Core 55 Core 66 CoreCore 7 7 CoreCore 8 8 Core 11 100%100% 86.7%86.7% 91.5%91.5% 86.1%86.1% 90.0%90.0% 90.9%90.9% 87.9%87.9% 86.7%86.7% Core 22 -- 100%100% 86.7%86.7% 87.9%87.9% 83.3%83.3% 83.9%83.9% 85.2%85.2% 87.9%87.9% Core 3 - - 100% 87.3% 90.6% 91.2% 92.8% 88.2% Core 43 -- -- 100 -% 87.3 100%% 84.6%90.6% 86.1%91.2% 84.9%92.8% 97.0%88.2% Core 54 -- -- -- 100 -% 84. 100%6% 90.3%86.1% 88.8%84.9% 85.8%97.0% Core 65 -- -- -- -- 100 -% 90.3 100%% 87.9%88.8% 87.6%85.8% Core 76 -- -- -- -- -- 100 -% 100%87.9% 85.8%87.6% Core 8 - - - - - - - 100% Core 7 - - - - - - 100% 85.8% Core 8 - - - - - - - 100% Table 2. Sequence identity matrix across capsid spike domains from human astrovirus serotypes 1–8. Table 2. SequenceSpike identity 1 Spike matrix 2 Spikeacross 3capsid Spike spike 4 domains Spike 5from Spike human 6 astrovirus Spike 7 serotypes Spike 8 1– 8. Spike 1 100% 50.2% 61.2% 41.4% 47.0% 53.1% 58.9% 53.0% Spike 2Spike - 1 Spike 100% 2 Spike 46.7% 3 Spike 47.9% 4 Spike 41.8% 5 Spike 47.0% 6 Spike 44.9% 7 Spike 49.8% 8 Spike 31 100 -% 50. -2% 61.2 100%% 41. 46.3%4% 4 48.6%7.0% 53. 54.7%1% 58. 75.7%9% 53.0 55.1%% Spike 4 - - - 100% 46.0% 47.0% 43.5% 46.1% Spike 52 -- 100 -% 46.7 -% 47.9 -% 41. 100%8% 63.34%47.0% 44. 52.8%9% 49. 52.1%8% Spike 63 -- - 100 -% 46. -3% 48. -6% 54.7 100%% 75. 56.6%7% 55.1 57.3%% Spike 74 -- - - 100 -% 46.0 -% 47.0 -% 43. 100%5% 46. 53.3%1% Spike 85 -- - - - 100 -% 63.3 -4% 52. -8% 52. 100%1% Spike 6 - - - - - 100% 56.6% 57.3% SpikeSerosurveillance 7 - investigations- - bring the- frequency- of previous- human100% astrovirus53.3% infectionSpike 8 in a particular- cohort- into focus,- but- only a few- have been- performed- on specific100% as- trovirus subsets (classical serotypes 1–7, MLB1, HMOAstV-C (VA1), or turkey astrovirus 2) or inSerosurveillance specific populations investigations (turkey growers bring andthe frequency abattoir workers) of previous (Table human3)[ 10 ,astrovirus23,31–36]. Manyinfection of thein a studies particular focusing cohort on into classical focus, but human only astrovirusa few have were been conductedperformed moreon specific than 20astrovirus years