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Mixed cytomegalovirus genotypes in HIV positive mothers show compartmentalization and distinct patterns of transmission to infants.
medRxiv - Genetic and Genomic Medicine Pub Date : 2020-09-18 , DOI: 10.1101/2020.09.17.20196790
Juanita Pang , Jennifer A. Slyker , Sunando Roy , Josephine Bryant , Claire Atkinson , Juliana Cudini , Carey Farquhar , Paul Griffiths , James Kiarie , Sofia Morfopoulou , Alison C. Roxby , Helena Tutill , Rachel Williams , Soren Gantt , Richard A. Goldstein , Judith Breuer

Cytomegalovirus (CMV) is the most congenital infection (cCMVi), and is particularly common among infants born to HIV-infected women. Studies of cCMVi pathogenesis are complicated by the presence of multiple infecting maternal CMV strains, especially in HIV-positive women, and the large, recombinant CMV genome. Using newly-developed tools to reconstruct CMV haplotypes, we demonstrate anatomic CMV compartmentalization in five HIV-infected mothers, and identify the possibility of congenitally-transmitted genotypes in three of their infants. A single CMV strain was transmitted in each congenitally-infected case, and all were closely related to those that predominate in the cognate maternal cervix. Compared to non-transmitted strains, these congenitally-transmitted CMV strains showed statistically significant similarities in 19 genes associated with tissue-tropism and immunomodulation. In all infants, incident superinfections with distinct strains from breast milk were captured during follow-up. The results represent potentially important new insights into the virologic determinants of early CMV infection.

中文翻译:

HIV阳性母亲的混合巨细胞病毒基因型表现出区室化和向婴儿传播的独特模式。

巨细胞病毒(CMV)是最先天性的感染(cCMVi),在感染了HIV的妇女所生的婴儿中尤为常见。cCMVi发病机制的研究由于存在多种感染性母体CMV菌株(尤其是在HIV阳性女性中)和庞大的重组CMV基因组而变得复杂。使用新开发的工具来重建CMV单倍型,我们证明了在5名受HIV感染的母亲体内的解剖性CMV分隔,并确定了其三名婴儿先天性传播基因型的可能性。在每个先天感染的病例中均传播了一个CMV毒株,并且全部与在母系子宫颈中占主导地位的那些密切相关。与非传播菌株相比,这些先天传播的CMV菌株在与组织嗜性和免疫调节相关的19个基因中显示出统计学上的显着相似性。在所有婴儿中,在随访期间均捕获了母乳中不同菌株的偶发性超级感染。这些结果代表了对早期CMV感染的病毒学决定因素的潜在重要的新见解。
更新日期:2020-09-20
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