Human Cytomegalovirus Genome Diversity in Longitudinally Collected Breast Milk Samples. BlooMil

Reactivation and shedding of human cytomegalovirus (HCMV) in breast milk during lactation is highly frequent in HCMV-seropositive mothers. This represents a key transmission route for postnatal HCMV infection, and can lead to severe disease in preterm neonates. Little is known about HCMV strain composition or intrahost viral population dynamics in breast milk from immunocompetent adults. We performed HCMV-specific target enrichment and high-throughput sequencing of 38 breast milk samples obtained in Germany between days 10 and 60 after giving birth from 15 mothers with HCMV DNA-lactia, and assembled HCMV consensus sequences de novo. The genotype distribution and number of HCMV strains present in each sample were determined by quantifying genotype-specific sequence motifs in 12 hypervariable viral genes, revealing a wide range of genotypes (82/109) for these genes in the cohort and unique, longitudinally stable strain compositions in each mother. Reactivation of up to three distinct HCMV strains was detected in 8/15 of mothers, with a statistical tendency for multiple-strain reactivations in mothers who had stated their country of origin as being outside Germany. As described previously, nucleotide diversity of samples with multiple strains was much higher than that of samples with single strains. Breast milk as a main source of postnatal transmission may serve as a repository for viral diversity and thus play an essential role in the natural epidemiology of HCMV.

哺乳期人巨细胞病毒（human cytomegalovirus, HCMV）在母乳中的再激活与排毒现象，在HCMV血清阳性母亲中极为常见。这是产后HCMV感染的关键传播途径，且可导致早产新生儿罹患重症疾病。目前对于免疫功能正常成人母乳中的HCMV毒株组成及宿主内病毒种群动态，人们尚所知甚少。本研究针对15名存在HCMV DNA母乳排毒的母亲，采集其产后10至60天内的38份母乳样本，开展HCMV特异性目标富集与高通量测序，并从头组装HCMV共识序列。通过对12个病毒高变基因中的基因型特异性序列基序进行定量分析，确定每份样本中的HCMV基因型分布与毒株数量。结果显示，本队列中这些基因存在82/109的广泛基因型谱系，且每名母亲的毒株组成均具有独特性与纵向稳定性。15名母亲中有8名可检测到最多3种不同HCMV毒株的再激活，且自述原籍非德国的母亲发生多毒株再激活的趋势具有统计学意义。如既往研究所述，多毒株样本的核苷酸多样性显著高于单毒株样本。作为产后传播的主要途径，母乳可作为病毒多样性的储存库，因此在HCMV的自然流行病学中发挥至关重要的作用。