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Notes: Abstract.  Lavas erupted behind the volcanic front in southeastern Guatemala have many important distinctions from lavas erupted on the volcanic front. These include: generally higher MgO, Nb, Sr, TiO2, and rare earth element concentrations; higher La/Yb and Nb/Y ratios; and lower Ba/La, La/Nb, Ba/Zr and Zr/Nb ratios. These major and trace element distinctions are caused by reduced fractionation during ascent and storage in the crust, lower degrees of melting in the source, and greatly reduced contributions from the subducted Cocos plate in the source. In addition, because all of these important distinctions are even borne in lavas erupted within 20 km of the front, there is little apparent petrogenetic continuity between front and behind-the-front magmas. What little geochemical continuity exists is in radiogenic isotopes: 143Nd/144Nd falls across the arc, Pb isotopic ratios (except 206Pb/204Pb) rise across the arc, and 87Sr/86Sr rise across the arc after an initial discontinuity within 20 km of the front. These continuous across-arc changes in radiogenic isotopes are caused by increased contamination with older, more isotopically disparate rocks, away from the front. Once the effects of crustal contamination are removed, the remaining isotopic variability behind the front is non-systematic and reflects the inherent isotopic heterogeneity of the source, the mantle wedge. Geochemical disconnection in southeastern Guatemala suggests that behind-the-front magmas are produced by decompression melting near the top of the wedge, not by flux-dominated melting near the base of the wedge.

Notes: Abstract Lavas erupted behind the volcanic front in southeastern Guatemala have many important distinctions from lavas erupted on the volcanic front. These include: generally higher MgO, Nb, Sr, TiO2, and rare earth element concentrations; higher La/Yb and Nb/Y ratios; and lower Ba/La, La/Nb, Ba/Zr and Zr/Nb ratios. These major and trace element distinctions are caused by reduced fractionation during ascent and storage in the crust, lower degrees of melting in the source, and greatly reduced contributions from the subducted Cocos plate in the source. In addition, because all of these important distinctions are even borne in lavas erupted within 20 km of the front, there is little apparent petrogenetic continuity between front and behind-the-front magmas. What little geochemical continuity exists is in radiogenic isotopes: 143Nd/144Nd falls across the arc, Pb isotopic ratios (except 206Pb/204Pb) rise across the arc, and 87Sr/86Sr rise across the arc after an initial discontinuity within 20 km of the front. These continuous across-arc changes in radiogenic isotopes are caused by increased contamination with older, more isotopically disparate rocks, away from the front. Once the effects of crustal contamination are removed, the remaining isotopic variability behind the front is non-systematic and reflects the inherent isotopic heterogeneity of the source, the mantle wedge. Geochemical disconnection in southeastern Guatemala suggests that behind-the-front magmas are produced by decompression melting near the top of the wedge, not by flux-dominated melting near the base of the wedge.

Notes: Summary A large placebo-controlled efficacy trial of the rhesus tetravalent (RRV-TV) and serotype G1 monovalent (RRV-S1) rotavirus vaccines was conducted in 1991–1992 at 24 sites across the United States. Protection was 49% and 54% against all diarrhea but 80% and 69% against very severe gastroenteritis for the two vaccines, respectively. Post-vaccination neutralizing antibody titers to the G1 Wa strain, whose VP7 protein is nearly identical to that of the D strain of rotavirus contained in both vaccines, did not correlate with protection against subsequent illness with G1 strains. This result raised the possibility that in infants who developed post-vaccination neutralizing antibody to Wa, breakthrough (i.e., vaccine failure—the occurrence of rotavirus diarrhea after immunization) may have been due to infection by G1 strains that were sufficiently antigenically distinct from the vaccine strain to evade the neutralizing antibodies elicited by vaccination. To test this hypothesis, we initially compared post-vaccination neutralizing antibody titers of vaccinees against Wa and G1 breakthrough strains using sera from subjects who experienced breakthrough. Post-immunization neutralizing antibody titers to Wa elicited by vaccination were significantly (P〈0.001) greater than to the breakthrough strains subsequently obtained from these subjects. This difference did not, however, correlate with lack of protection since similar differences in titer to Wa and breakthrough strains were found using post-vaccination sera from vaccinees who either experienced asymptomatic rotavirus infections or no infections. To determine the genetic basis for these differences, we compared the VP7 gene sequences of Wa with vaccine strain D, 12 G1 breakthrough strains, and 3 G1 control strains isolated during the same trial from placebo recipients. All breakthrough strains were distinct from Wa and D in antigenically important regions throughout the VP7 protein, but these differences were conserved between breakthrough and placebo strains. Furthermore, a comparative analysis of the deduced amino sequences from VP7 genes of G1 rotaviruses from 12 countries indicated that four distinct lineages have evolved. All breakthrough and control strains from the U.S. vaccine trial were in a lineage different from strain D, the serotype G1 vaccine strain. Although the overall results do not support our original hypothesis that immune selection of antigenically distinct escape mutants led to vaccine breakthrough in subjects with a neutralization response to Wa, it cannot be excluded that breakthrough could be partially due to antigenic differences in the VP7 proteins of currently circulating G1 strains.

Notes: Summary Bovine-human reassortant strains containing ten human rotavirus gene segments and segment 4, encoding VP4, of a bovine rotavirus were isolated from the stool of an infected Bangladeshi infant during cell culture adaptation. Two plaque purified variants of this reassortant, one making very large (429-L4) and the other tiny (429-S4) plaques, were further analyzed. The electropherotypes of these variants were identical except for slight mobility differences in segment 4. The predicted sequence of amino acids (aa) 16–280 in VP4 proteins revealed four differences between variants even in this limited region, so no single difference could be linked to plaque size. The small plaque variant S4 was phenotypically unstable and mutated to a large plaque-former within a single cell culture passage. The predicted sequence of aa 16–280 of a large plaque variant derived from S4 revealed six changes, only one of which was common to that of the L4 strain, thus suggesting that multiple amino acid changes in VP4 may affect plaque size. Although the large plaque variant L4 grew faster and was released from cells more rapidly than S4, its replication and that of other rotaviruses tested (i.e. RRV, NCDV and Wa) was suppressed by S4 in coinfected cells. Using an RRV×S4 reassortant containing only RRV segment 4, it was established that suppression was linked to the S4 VP4 protein. This suppression could not be associated with inhibition of viral adsorption and, therefore, appeared to occur following internalization. Thus, a new property of the rotavirus VP4 protein has been identified in a bovine-human rotavirus reas-sortant.

Notes: Summary Culture adaptation of rotavirues from an infant with severe diarrhea in Cincinnati, Ohio, yielded not only a virus with the original RNA electropherotype (CJN) but also rotaviruses with other electropherotypes, the most dominant of which was called CJN-M [Ward RL, Knowlton DR, Schiff GM, Hoshino Y, Greenberg HB (1988) in J Virol 62: 1543–1549]. RNA-RNA hybridization and sequencing studies indicated that CJN was a typical G1P8 human rotavirus while CJN-M was a G1P5 strain and contained four gene segments (including segment 4) of a bovine rotavirus. Thus, the infant was apparently dually infected with human and bovine rotaviruses.