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Relationships Between Maternal Antibody Responses and Early Childhood Infection With Kaposi Sarcoma-Associated Herpesvirus.

ABSTRACT: While mother-to-child transmission is believed to play in important role in early childhood infection with Kaposi sarcoma-associated herpesvirus (KSHV), the maternal immune response remains largely uncharacterized. This study aimed to characterize the longitudinal humoral response to KSHV in a cohort of HIV-infected Zambian mothers without KS and identify potential factors that may influence transmission. In total, 86/124 (69.4%) mothers were found to be KSHV seropositive. Longitudinal KSHV titers were fairly stable over time, although seroreversion was still common. Of the total 124 mothers, 81 had at least 1 child KSHV seroconvert during the 2 years analyzed, while the remaining 43 mothers had KSHV-seronegative children. Mothers of KSHV-negative children had higher geometric mean titers than mothers of KSHV-positive children; however, there was no difference in the presence of neutralizing antibodies. This suggests that a strong anti-KSHV immune response, and potentially nonneutralizing antibodies, may reduce transmission.

SUBMITTER: Poppe LK

PROVIDER: S-EPMC7982718 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Intra-host tumor virus variants may influence the pathogenesis and treatment responses of some virally-associated cancers. However, the intra-host variability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma (KS), has to date been explored with sequencing technologies that possibly introduce more errors than that which occurs in the viral population, and these studies have only studied variable regions. Here, full-length KSHV genomes in tumors and/or oral swabs from 9 Ugandan adults with HIV-associated KS were characterized. Furthermore, we used deep, short-read sequencing using duplex unique molecular identifiers (dUMI)-random double-stranded oligonucleotides that barcode individual DNA molecules before library amplification. This allowed suppression of PCR and sequencing errors to ~10-9/base as well as afforded accurate determination of KSHV genome numbers sequenced in each sample. KSHV genomes were assembled de novo, and rearrangements observed were confirmed by PCR and Sanger sequencing. 131-kb KSHV genome sequences, excluding major repeat regions, were successfully obtained from 23 clinical specimens, averaging 2.3x104 reads/base. Strikingly, KSHV genomes were virtually identical within individuals at the point mutational level. The intra-host heterogeneity that was observed was confined to tumor-associated KSHV mutations and genome rearrangements, all impacting protein-coding sequences. Although it is unclear whether these changes were important to tumorigenesis or occurred as a result of genomic instability in tumors, similar changes were observed across individuals. These included inactivation of the K8.1 gene in tumors of 3 individuals and retention of a region around the first major internal repeat (IR1) in all instances of genomic deletions and rearrangements. Notably, the same breakpoint junctions were found in distinct tumors within single individuals, suggesting metastatic spread of rearranged KSHV genomes. These findings define KSHV intra-host heterogeneity in vivo with greater precision than has been possible in the past and suggest the possibility that aberrant KSHV genomes may contribute to aspects of KS tumorigenesis. Furthermore, study of KSHV with use of dUMI provides a proof of concept for utilizing this technique for detailed study of other virus populations in vivo.

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Relationships Between Maternal Antibody Responses and Early Childhood Infection With Kaposi Sarcoma-Associated Herpesvirus.

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