Palmenberg, A. | bioRxiv Science

bioRxiv2023

Assessing Immune Factors in Maternal Milk and Paired Infant Plasma Antibody Binding to Human Rhinoviruses

Before they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia. We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11. Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C dominant protein loop sequences characteristic of this species capsid VP1 protein. Many of these RV-C sites were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.

immunology↗

bioRxiv2017

Evolutionary Genetics of a Disease Susceptibility Locus in CDHR3

Selective pressures imposed by pathogens have varied among human populations throughout their evolution, leading to marked inter-population differences at some genes mediating susceptibility to infectious and immune-related diseases. A common polymorphism resulting in a C529 versus T529 change in the Cadherin-Related Family Member 3 (CDHR3) receptor is associated with rhinovirus-C (RV-C) susceptibility and severe childhood asthma. Given the morbidity and mortality associated with RV-C dependent respiratory infections and asthma, we hypothesized that the protective variant has been under selection in the human population. Supporting this idea, a recent cross-species outbreak of RV-C among chimpanzees in Uganda, which carry the ancestral risk allele at this position, resulted in a mortality rate of 8.9%. Using publicly available genomic data, we sought to determine the evolutionary history and role of selection acting on this infectious disease susceptibility locus. The protective variant is the derived allele and is found at high frequency worldwide, with the lowest relative frequency in African populations and highest in East Asian populations. There is minimal population structure among haplotypes, and we detect genomic signatures consistent with a rapid increase in frequency of the protective allele across all human populations. However, given strong evidence that the protective allele arose in anatomically modern humans prior to their migrations out of Africa and that the allele has not fixed in any population, the patterns observed here are not consistent with a classical selective sweep. We hypothesize that patterns may indicate frequency-dependent selection worldwide. Irrespective of the mode of selection, our analyses show the derived allele has been subject to selection in recent human evolution.

genetics↗