Serological Studies Confirm the Novel Astrovirus HMOAstV-C as a Highly Prevalent Human Infectious Agent

Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS ONE (Impact Factor: 3.23). 08/2011; 6(8):e22576. DOI: 10.1371/journal.pone.0022576
Source: PubMed


Molecular identification of a microbe is the first step in determining its prevalence of infection and pathogenic potential. Detection of specific adaptive immune responses can provide insights into whether a microbe is a human infectious agent and its epidemiology. Here we characterized human anti-IgG antibody responses by luciferase immunoprecipitation systems (LIPS) against two protein fragments derived from the capsid protein of the novel HMOAstV-C astrovirus. While antibodies to the N-terminal fragment were not informative, the C-terminal capsid fragment of HMOAstV-C showed a high frequency of immunoreactivity with serum from healthy blood donors. In contrast, a similar C-terminal capsid fragment from the related HMOAstV-A astrovirus failed to show immunoreactivity. Detailed analysis of adult serum from the United Sates using a standardized threshold demonstrated HMOAstV-C seropositivity in approximately 65% of the samples. Evaluation of serum samples from different pediatric age groups revealed that the prevalence of antibodies in 6-12 month, 1-2 year, 2-5 year and 5-10 year olds was 20%, 23%, 32% and 36%, respectively, indicating rising seroprevalence with age. Additionally, 50% (11/22) of the 0-6 month old children showed anti-HMOAstV-C antibody responses, likely reflecting maternal antibodies. Together these results document human humoral responses to HMOAstV-C and validate LIPS as a facile and effective approach for identifying humoral responses to novel infectious agents.

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    • "HAstV-VA1 was reported as the causative agent for a diarrhea outbreak in a child care center in Virginia [5]. Serological studies showed HAstV-HMO-C to be a highly prevalent human infection [7] with approximately 65% of adult in the US showing antibody reactivity. Recently HAstV-VA4 was discovered in diarrhea from Nepalese children with a prevalence of 1% (2/196) [6]. "
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    ABSTRACT: Background A significant fraction of cases of diarrhea, a leading cause of childhood mortality worldwide, remain unexplained. Objectives To identify viruses in unexplained cases of diarrhea using an unbiased metagenomics approach. Study design Viral nucleic acids were enriched from the feces from 48 cases of unexplained diarrhea from Burkina Faso, sequenced, and compared against all known viral genomes. Results The full genome of a highly divergent astrovirus was sequenced in a sample co-infected with parechovirus 1. RT-PCR identified a single astrovirus infection in these 48 patients indicating a low prevalence. Human astrovirus-BF34 was most closely related to mamastrovirus species 8 and 9 also found in human with which it shared 62%, 74%, and 57% amino acid identities over its protease, RNA dependent RNA polymerase and capsid proteins, respectively. Conclusions Burkina Faso astrovirus is proposed as prototype for a novel species in the genus Mamastrovirus, here tentatively called Mamastrovirus 20, representing the fifth human astrovirus species.
    Full-text · Article · Jun 2014 · Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology
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    • "Many of the LIPS antigens used for the infectious agents described above have been previously reported along with their diagnostic performance including the gG-1 of herpes simplex virus-1 (HSV-1) [19], gG-2 of herpes simplex virus-2 (HSV-2) [19], BFRF3 (p18), BZLF2, BHRF1, and BMRF1 of Epstein-Barr virus (EBV) [20], pp165 and pp65 of Cytomegalovirus (CMV) [21], p101 of Human herpes virus-6B (HHV-6) [22] , HA2 of influenza [20], capsid of HMO-astrovirus [23] and the MSG-14 of Pneumocystis jirovecii [24]. New antigen constructs for additional infectious agent targets were chosen based on their known antigenicity and were generated essentially as described using the pREN2 and pREN3S vector [24]. "
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    ABSTRACT: Despite the important diagnostic value of evaluating antibody responses to individual human pathogens, antibody profiles against multiple infectious agents have not been used to explore health and disease mainly for technical reasons. We hypothesized that the interplay between infection and chronic disease might be revealed by profiling antibodies against multiple agents. Here, the levels of antibodies against a panel of 13 common infectious agents were evaluated with the quantitative Luciferase Immunoprecipitation Systems (LIPS) in patients from three disease cohorts including those with pathogenic anti-interferon-γ autoantibodies (IFN-γ AAB), HIV and Sjögren's syndrome (SjS) to determine if their antibody profiles differed from control subjects. The IFN-γ AAB patients compared to controls demonstrated statistically higher levels of antibodies against VZV (p=0.0003), EBV (p=0.002), CMV (p=0.003), and C. albicans (p=0.03), but lower antibody levels against poliovirus (p=0.04). Comparison of HIV patients with blood donor controls revealed that the patients had higher levels of antibodies against CMV (p=0.0008), HSV-2 (p=0.0008), EBV (p=0.001), and C. albicans (p=0.01), but showed decreased levels of antibodies against coxsackievirus B4 (p=0.0008), poliovirus (p=0.0005), and HHV-6B (p=0.002). Lastly, SjS patients had higher levels of anti-EBV antibodies (p=0.03), but lower antibody levels against several enteroviruses including a newly identified picornavirus, HCoSV-A (p=0.004), coxsackievirus B4 (p=0.04), and poliovirus (p=0.02). For the IFN-γ AAB and HIV cohorts, principal component analysis revealed unique antibody clusters that showed the potential to discriminate patients from controls. The results suggest that antibody profiles against these and likely other common infectious agents may yield insight into the interplay between exposure to infectious agents, dysbiosis, adaptive immunity and disease activity.
    Full-text · Article · Dec 2013 · PLoS ONE
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    • "HAstV-PS was the only virus detected, and astrocyte infection was confirmed by anticapsid antibody staining (6). Serologic evidence of exposure to the closely related AstV-HMO-C was found in 36% of 5–10-year-old children in the United States, which reflects a common childhood infection and indicates that the encephalitis in this child was a likely consequence of his immunodeficiency (9). In an outbreak of so-called “neurological shaking disease” in mink, an astrovirus (Mink AstV-SMS) was detected in the brain tissues of multiple naturally and experimentally infected animals showing neurologic signs, including shaking and ataxia (5). "
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    ABSTRACT: Using viral metagenomics of brain tissue from a young adult crossbreed steer with acute onset of neurologic disease, we sequenced the complete genome of a novel astrovirus (BoAstV-NeuroS1) that was phylogenetically related to an ovine astrovirus. In a retrospective analysis of 32 cases of bovine encephalitides of unknown etiology, 3 other infected animals were detected by using PCR and in situ hybridization for viral RNA. Viral RNA was restricted to the nervous system and detected in the cytoplasm of affected neurons within the spinal cord, brainstem, and cerebellum. Microscopically, the lesions were of widespread neuronal necrosis, microgliosis, and perivascular cuffing preferentially distributed in gray matter and most severe in the cerebellum and brainstem, with increasing intensity caudally down the spinal cord. These results suggest that infection with BoAstV-NeuroS1 is a potential cause of neurologic disease in cattle.
    Full-text · Article · Sep 2013 · Emerging Infectious Diseases
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