The genome of rotaviruses consists of 11 segments of double-stranded RNA, and each genome segment has multiple genotypes. Thus, the genotype constellation of an isolate is often indicative of its host species. Albeit rarely, interspecies transmission occurs either by virions with nonreassorted or reassorted genomic segments. A rotavirus with the G6P[1] genotype, Ro8059, was isolated from the stool of a 1-year-old child during routine characterization of diarrheal specimens from a sentinel clinic in Israel in 1995. Since genotype G6P[1] is generally associated with bovine rotaviruses, and the child developed diarrhea within days of his first contact with calves at an urban farm, the aim of this study was to characterize the whole genomic constellation of Ro8059 and four G6P[1] bovine strains, BRV101, BRV105, BRV106, and CR231/39, by RNA-RNA hybridization and full genome sequencing to determine whether some or all of the segments were of bovine origin. The genome constellations of all four bovine G6P[1] strains were G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3 for VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5, respectively. Ro8059 shared the same genotype constellation with these bovine strains, with high nucleotide sequence identities (95.84 to 100%) for each of the 11 segments indicating that Ro8059 represented a direct interspecies whole-genome transmission of a nonreassorted rotavirus from a calf to a human infant. We conclude that this was the earliest example with a complete epidemiological link in which an entirely bovine rotavirus directly infected a human child and caused a symptomatic diarrheal illness. Thus, not all bovine rotaviruses are always naturally attenuated to the human host.

An unusual, highly diverged derivative of the Sabin type 2 oral poliovaccine (OPV) strain was recovered from environmental samples during routine screening for wild polioviruses. Virus was cultivated in L20B cells and then passaged on BGM cells at 40°C (RCT [reproductive capacity at supraoptimal temperature]-positive marker) to select against most OPV strains. All but 1 of 25 RCT-positive OPV-derived environmental isolates were antigenically and genetically (>99.5% VP1 sequence match) similar to the respective Sabin strains. However, isolate PV2/4568-1/ISR98 (referred to below as 4568-1) escaped neutralization with Sabin 2-specific monoclonal antibodies and cross-adsorbed sera, and had multiple nucleotide substitutions (220 of 2,646; 8.3%) in the P1 capsid region. Fourteen of the 44 associated amino acid substitutions in the capsid mapped to neutralizing antigenic sites. Neutralizing titers in the sera of 50 Israeli children 15 years old were significantly lower to 4568-1 (geometric mean titer [GMT], 47) than to Sabin 2 (GMT, 162) or to the prototype wild strain, PV2/MEF-1/EGY42 (GMT, 108). Two key attenuating sites had also reverted in 4568-1 (A 481 to G in the 5 untranslated region and the VP1 amino acid I 143 to T), and the isolate was highly neurovirulent for transgenic mice expressing the poliovirus receptor (PVR-Tg21 mice). The extensive genetic divergence of 4568-1 from the parental Sabin 2 strain suggested that the virus had replicated in one or more people for ϳ6 years. The presence in the environment of a highly evolved, neurovirulent OPV-derived poliovirus in the absence of polio cases has important implications for strategies for the cessation of immunization with OPV following global polio eradication.

The VP4 protein of human rotavirus (HRV) strain Ro1845 and canine rotavirus strains K9 and CU-1 exhibited greater than 98 % amino acid identity within their group, but showed less identity with VP4 proteins of other HRV and animal rotavirus strains, the simian rotavirus strain RRV VP4 being most similar to them (90 % amino acid identity). To exclude the possibility that these three strains were members of the RRV VP4 serotype P3, neutralization studies were performed using antisera to reassortant viruses containing the VP4 gene from each of Ro1845, CU-1 and RRV. The result established close antigenic similarity among the VP4 proteins of Ro1845, K9 and CU-1 and revealed only a marginal degree of similarity between the VP4 proteins of these three strains and that of strain RRV. These sequence and serological data suggest that the VP4 proteins of Ro1845, K9 and CU-1 represent a new P serotype which we propose to assign P13.

Human rotaviruses belonging to genotype P9, of probable feline origin, which included both G3 and G1 serotypes, were detected in 3.8% of children shedding rotaviruses who attended sick fund clinics throughout Israel. None were detected in children admitted to hospitals because of severe diarrhea. In contrast, the relative prevalences of genotypes P8 and P4 were similar between the two groups. The two outer capsid viral proteins VP7 and VP4 form the basis for the current classification of group A rotaviruses into G (VP7) and P (VP4) serotypes (4). To date, 14 G serotypes (1, 2, 4) and at least 18 P serotypes (19, 21) have been recognized among field isolates of animal and human rotaviruses. A distinction between P serotypes and P genotypes has been suggested (19). A P genotype includes group A rotaviruses having homology of 89% or greater in the deduced amino acid sequences of their VP4. A P serotype relates to group A rotaviruses shown to be related by one-way neutralization or crossneutralization. Because of lack of data, not all P genotypes have been assigned a P serotype yet. Serotypes G1 to G4 (4) and genotypes P8 (Wa-like) and P-4 (DS-1-like) (9, 19) are widespread among human populations. Other human G serotypes and P genotypes, such as G8, G9, and G12 and such as P6 (M37-like) and P10 (69M-like), are less frequent. However, G serotypes 5, 6, and 10, which were thought to be exclusively animal viruses, have recently been recovered from children with diarrhea and from asymptomatic neonates (3, 8, 10). Certain P genotypes were also detected in both animals and humans. These included genotype P9 (AU-1-like), which specifies the AU-1 VP4 allele and was detected in both cats and humans (13). Another P genotype, P13 (HCR-3-like or Ro-1845-like), is common to all canine and certain feline rotaviruses and was also detected in human babies in Israel, the United States, and Brazil (14, 15, 22). Finally, genotype P11 (B-223-like), a bovine rotavirus, was detected in asymptomatic neonates in India (3, 6). Several panels of G serotype-specific monoclonal antibodies are now available, but P serotype-specific monoclonal antibodies are harder to obtain. Consequently, investigators use cDNA probes made up from highly divergent and serotype-specific regions in gene 4 (20), the gene encoding the VP4 protein, and PCR techniques (7, 11, 18) in order to classify field isolates of rotaviruses into P genotypes. We undertook this study in order to find out whether the distribution of rotavirus G serotypes and P genotypes in the community differed from that among hospitalized children with diarrhea. Stool samples were collected between September 1991 and August 1994 from children 2 months to 4 years of age who were hospitalized in four major and two smaller hospitals in Israel because of severe diarrhea or who presented at 15 sick