ABSTRACT
Background In developed countries, human cytomegalovirus, HCMV, is a major pathogen in congenitally infected people and immunocompromised individuals, where multiple-strain infections link with disease severity. The situation is less understood in developing countries. In Zambia, breast milk, a key route for transmission, carries higher HCMV loads in HIV-positive than HIV-negative women. We investigated whether strain diversity was also higher.
Methods Strain diversity in breast milk obtained 4-16 weeks post-partum from 15 HIV-positive and 7 HIV-negative women was analysed by high-throughput sequencing, comparison to 100+ reference genomes and genotyping of hypervariable genes.
Results Multiple-strain infections were detected in 100% HIV-positive and 43% HIV-negative women, showing raised strain-diversity burden with HIV (p=0.005) and up to 6 strains, present in serial samples. There were 95 genotypes in 12 hypervariable genes, combined in 30 strains; these were conserved within individuals, but gave potential for billions of recombinants. Genetic linkage was maintained strongly for adjacent genes UL73/UL74 (encoding entry/exit glycoproteins gN/gO), and RL12/RL13 /UL1 (encoding immunomodulatory glycoproteins), but not for other nonadjacent genes.
Conclusions Breast milk is infected with multiple-strains of HCMV in HIV-infected women in Zambia. The complexity provides capacity for generating large numbers of recombinant strains and a major source for transmitting diversity.
Footnotes
↵* Present affiliation: Public Health England, Porton Down, Wiltshire, United Kingdom
Financial support. This work was supported by the Commonwealth Scholarship Commission, a Bloomsbury Studentship Award and the Medical Research Council (programme grant MC_UU_12014/3).
Potential conflicts of interest. The authors report no conflicts of interest in this study.