CORRELATION OF PATIENT IMMUNE-RESPONSES WITH GENETICALLY CHARACTERIZED SMALL ROUND-STRUCTURED VIRUSES INVOLVED IN OUTBREAKS OF NONBACTERIALACUTE GASTROENTERITIS IN THE UNITED-STATES, 1990 TO 1995

Small round-structured viruses (SRSVs) are a genetically and antigenic ally diverse group of caliciviruses that are the most common cause of outbreaks of acute nonbacterial gastroenteritis. We have applied both molecular techniques to characterize SRSVs in fecal specimens and sero logic assays using four different expressed SRSV antigens to examine t he distribution of outbreak strains in the United States and determine if the immune responses of patients were strain specific. Strains fro m 23 outbreaks of SRSV gastroenteritis were characterized by reverse t ranscription-PCR and nucleotide sequencing of a 277-base region of the capsid gene. These strains segregated into two distinct genogroups, I and II, comprising four and six clusters of strains respectively, eac h representing a distinct phylogenetic lineage. Serum IgG responses in patients were measured by enzyme immunoassay using expressed capsid a ntigens of Norwalk virus (NV), Toronto virus (TV), Hawaii virus (HV), and Lordsdale virus (LV), representing four of the 10 clusters. While strains in genogroups I and II were antigenically distinct, within gen ogroups, the specificity of the immune response varied greatly. Patien ts infected with genogroup I strains which had as much as 38.5% aa div ergence from NV demonstrated relatively homologous seroresponses to th e single NV antigen. In contrast, in genogroup II, homologous seroresp onses to TV and HV were only present when the infecting strains showed less than 6.5% aa divergence from these antigens. These results sugge st that TV and HV represent not only separate genetic clusters in geno group II but also separate antigenic groups, each of which is related but distinguishable. In addition, two genetically distinct SRSV strain s were identified for which we have no homologous antigen. This study suggests that while current molecular diagnostics are capable of detec ting the full range of SRSVs, additional expressed antigens will be re quired to detect an immune response to SRSV infection caused by all th e antigenically diverse strains. (C) 1997 Wiley-Liss, Inc.