Summary
Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals that develop high titers of anti-ZIKV antibodies we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes. These recurring antibodies cross-react with DENV1, but not other flaviviruses, neutralize both DENV1 and ZIKV, and protect mice against ZIKV challenge. Structural analyses reveal the mechanism of recognition of the ZEDIII lateral ridge by VH3-23/VK1-5 antibodies. Serologic testing shows that antibodies to this region correlate with serum neutralizing activity to ZIKV. Thus, high neutralizing responses to ZIKV are associated with preexisting reactivity to DENV1 in humans.
Previously, we identified the glycoprotein gO gene, UL74, as a hypervariable locus in the human cytomegalovirus (HCMV) genome [Virology 293 (2002) 281]. Here, we analyze gO from 50 isolates from congenitally infected newborns, transplant recipients, and HIV/AIDS patients from Italy, Australia, and UK. These are compared to four gO groups described from USA transplantation patients [J. Virol. 76 (2002) 10841]. Phylogenetic analyses identified seven genotypes. Divergence between genotypes was up to 55% and within 3%. Discrete linkage was shown between seven hypervariable gO and gN genotypes, but not with gB. This suggests interactions, while gN and gO are known to form complexes with distinct conserved glycoproteins gM, gH/gL, respectively, both are involved in fusogenic entry and exit. Codon-based maximum likelihood models showed evidence for sites of positive selection. Further analyses of disease relationships should take into account these newly defined gO/gN groups.
To date, mother-to-fetus transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19) pandemic, remains controversial. Although placental COVID-19 infection has been documented in some cases during the second-and third-trimesters, no reports are available for the first trimester of pregnancy, and no SARS-CoV-2 protein has been found in fetal tissues. We studied the placenta and fetal organs from an early pregnancy miscarriage in a COVID-19 maternal infection by immunohistochemical, reverse
A cell fusion assay using fusion-from-without (FFWO) recombinant adenoviruses (RAds) and specific antibody showed a role in fusion modulation for glycoprotein gO, the recently identified third component of the gH/gL gCIII complex of human cytomegalovirus (HCMV). As in HCMV, RAd gO expressed multiple glycosylated species with a mature product of 125 kDa. Coexpression with gH/gL RAds showed gCIII reconstitution in the absence of other HCMV products and stabilisation by intermolecular disulfide bonds. Properties of HCMV clinical isolate, Pt, also implicated gO in cell spread. Compared to laboratory strain AD169, Pt was resistant to gH antibody plaque inhibition, but mature gH was identical. However, the gO sequences were highly divergent (20%), with further variation in laboratory strain Towne gO (34%). Thus, gO forms gCIII with gH/gL, performs in cell fusion, and is a newly identified HCMV hypervariable locus which may influence gCIII's function in mediating infection.
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