High Prevalence of Distinct Human Herpesvirus 8 Contributes to the High Incidence of Non-acquired Immune Deficiency Syndrome-Associated Kaposi’s Sarcoma in Isolated Japanese Islands

Awazawa, Ryoko; Utsumi, Daisuke; Katano, Harutaka; Awazawa, Tsuyoshi; Miyagi, Takuya; Hayashi, Kentarō; Matori, Shigetaka; Uezato, Hiroshi; Takahashi, Keiichi

doi:10.1093/infdis/jix424

Cited by 21 publications

(16 citation statements)

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“…These genomes corresponded to K1 subtypes A5, B1 and C3 ( S5A Fig ) and K15 alleles P and M ( S5B Fig ). While K1 and K15 are the most variable KSHV genes, polymorphisms along the rest of the genome have been reported to contribute more in aggregate to the total diversity of KSHV [33,34,36]. Consistent with this, maximum-likelihood phylogenetic trees using entire KSHV genomes ( S5C Fig ) were topologically distinct from those of K1 or K15.…”

Section: Resultsmentioning

confidence: 53%

“…KSHV whole genome sequences provide a far more comprehensive picture of KSHV diversity than the KSHV variable regions alone. Most of the publicly available KSHV genomes have been reported in only the last 5 years [33–37], and they demonstrated that polymorphisms in the ∼130-kb KSHV non-repeat genomic region outside of the K1 gene contribute much more to KSHV diversity than the 0.9 kb hyper-variable K1 gene by itself [33,34]. KSHV genomes are, moreover, replete with signatures of recombination [36], potentially complicating disease risk association solely with K1 subtypes.…”

Section: Introductionmentioning

confidence: 99%

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Tumor-specific changes in Kaposi sarcoma-associated herpesvirus genomes in Ugandan adults with Kaposi sarcoma

Santiago

Goldman

Zhao

et al. 2020

Preprint

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Intra-host evolved tumor virus variants have provided insights into the risk, pathogenesis and treatment responses of associated cancers. However, the intra-host variability of Kaposi sarcoma-associated herpesvirus (KSHV), the etiologic agent of Kaposi sarcoma (KS), has not been explored at the whole viral genome level. An accurate and detailed description of KSHV intra-host diversity in whole KSHV genomes from matching tumors and oral swabs from Ugandan adults with HIV-associated KS was obtained by 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 down to ∼10−9/base. KSHV genomes were assembled de novo, and identified rearrangements were confirmed by PCR. 131-kb KSHV genome sequences, excluding major repeat regions and averaging 2.3 × 104 reads/base, were successfully obtained from 23 specimens from 9 individuals, including 7 tumor-oral pairs. Sampling more than 100 viral genomes in at least one specimen per individual showed that KSHV genomes were virtually homogeneous within samples and within individuals at the point mutational level. Heterogeneity, if present, was due to point mutations and genomic rearrangements in tumors. In 2 individuals, the same mutations were found in distinct KS tumors. The K8.1 gene was inactivated in tumors from 3 individuals, and all KSHV genomic aberrations retained the region surrounding the first major internal repeat (IR1). These findings suggest that lytic gene alterations may contribute to KS tumorigenesis or persistence.Author summaryKaposi sarcoma (KS) is a leading cancer in sub-Saharan Africa and in those with HIV co-infection. Infection by Kaposi sarcoma-associated herpesvirus (KSHV) is necessary for KS, yet why only few KSHV infections develop into KS is largely unknown. While strain differences or mutations in other tumor viruses are known to affect the risk and progression of their associated cancers, whether KSHV genetic variation is important to the natural history of KS is unclear. Most studies of KSHV diversity have characterized only ∼4% of its 165-kb genome and may have been impacted by PCR or cloning artifacts. Here, we performed highly sensitive, single-molecule sequencing of whole KSHV genomes in paired KS tumors and oral swabs from 9 individuals with KS. We found that KSHV genomes were virtually identical within individuals, with no evidence of quasispecies formation nor multistrain infection. However, KSHV genome aberrations and inactivating mutations appeared to be a common, tumor-associated phenomenon, with some mutations shared by distinct tumors within an individual. Certain regions of the KSHV genome featured prominently among tumor-associated mutations, suggesting that they are important contributors to the pathogenesis or persistence of KS.

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Section: Resultsmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Tumor-specific changes in Kaposi sarcoma-associated herpesvirus genomes in Ugandan adults with Kaposi sarcoma

Santiago

Goldman

Zhao

et al. 2020

Preprint

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“…After that, other reports described "solid tumors" that also occurred in patients with KS as SPMs [6,34]. KS is a rare disease; therefore, patients in previous studies should be reviewed to identify its characteristics [35]. Table 1 shows that more than 280 patients with KS (including our case) had solid malignancy associated with head and neck, esophagus, stomach, duodenum, or colorectal cancer.…”

Section: Discussionmentioning

confidence: 85%

Quadruple Multiple Primary Malignancies: Early Detection of Second Primary Malignancy by Esophagogastroduodenoscopy/Colonoscopy Is Crucial for Patients with Classic Kaposi’s Sarcoma

et al. 2020

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Currently, Kaposi’s sarcoma (KS) is treated following the recommendations of international guidelines. These guidelines recommend esophagogastroduodenoscopy/colonoscopy for detecting multicentric KS of visceral lesions. Second primary malignancies (SPMs) are also a common KS complication; however, information on their detection and treatment is unfortunately not yet indicated in these guidelines. This paper reports on an 86-year-old man who suffered from quadruple primary malignancies: skin classic KS with colon adenocarcinoma, oral squamous cell carcinoma (maxilla), and well-differentiated stomach adenocarcinoma. Gastric cancer was incidentally detected during esophagogastroduodenoscopy, which was performed to detect visceral KS. We suggest that esophagogastroduodenoscopy/colonoscopy be routinely performed during the follow-up of patients with KS. As SPMs are crucial complications in patients with KS, these malignancies should be detected as early as possible.

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“…In Sub‐Saharan Africa where there is a high incidence of African endemic KS, the seroprevalence of KSHV in the general population ranges from 30% to 80% . In North American, Europe, and most Asia regions where there is traditionally a low incidence of KS, the seroprevalence of KSHV is relatively low in the general population …”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10][11] In North American, Europe, and most Asia regions where there is traditionally a low incidence of KS, the seroprevalence of KSHV is relatively low in the general population. 6,12,13 In most provinces of China, the seroprevalence of KSHV is less than 11% in the general population. [13][14][15] However, Xinjiang Uygur autonomous region, located in northwestern China and diverse in ethnicity, has a significantly higher incidence of KS and a higher seroprevalence of KSHV.…”

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confidence: 99%

Social behavioral correlates of Kaposi sarcoma–associated herpesvirus infection among Han and Uygur populations in Xinjiang, China

Yuan

Liu

et al. 2018

Journal of Medical Virology

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Background Kaposi sarcoma–associated herpesvirus (KSHV) is endemic in Xinjiang, China and its prevalence varies considerably across ethnic groups. The current study explored the prevalence and correlates of KSHV infection among Han and Uygur populations in Xinjiang. Methods A cross‐sectional study, including 282 Han ethnicity and 312 Uygur, was conducted in Xinjiang, China. All participants underwent face to face questionnaire interview. Plasma samples were collected and screened for KSHV infection using immunofluorescence assay. Univariate and multivariate analyses were conducted to examine the correlates of KSHV seropositivity. Results The KSHV seroprevalence was 41.6% (95% confidence interval [CI], 37.6‐45.6) overall and was higher in the Uygur group (59.9%; 95% CI, 54.3‐65.4) than the Han group (21.3%; 95% CI, 16.6‐26.5). A significant difference in the geometric mean titer (GMT) of the KSHV antibodies was detected between the Uygur and Han groups (158.2; interquartile range [IQR], 80‐320 vs 89.1; IQR, 40‐160; P < 0.001). After adjusting for potential confounders, Uygur ethnicity (odds ratios [OR], 5.96; 95% CI, 4.05‐8.90), age greater than or equal to 50 years (OR, 1.84; 95% CI, 1.24‐2.77), and preference for meat diet (OR, 2.15; 95% CI, 1.05‐4.46) were significantly associated with increased odds of KSHV seropositivity. Conclusion The study demonstrated high prevalence and correlates of KSHV infection in both Han and Uygur populations in Xinjiang, China. There is an urgent need for programmatic adaptation to address primary prevention interventions of KSHV infection in this endemic region.

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High Prevalence of Distinct Human Herpesvirus 8 Contributes to the High Incidence of Non-acquired Immune Deficiency Syndrome-Associated Kaposi’s Sarcoma in Isolated Japanese Islands

Abstract: Miyako Islands are an endemic area of non-AIDS KS. The high rate of a distinct HHV8 may contribute to the high incidence of KS in the region.

Cited by 21 publications

References 44 publications

Tumor-specific changes in Kaposi sarcoma-associated herpesvirus genomes in Ugandan adults with Kaposi sarcoma

Tumor-specific changes in Kaposi sarcoma-associated herpesvirus genomes in Ugandan adults with Kaposi sarcoma

Quadruple Multiple Primary Malignancies: Early Detection of Second Primary Malignancy by Esophagogastroduodenoscopy/Colonoscopy Is Crucial for Patients with Classic Kaposi’s Sarcoma

Social behavioral correlates of Kaposi sarcoma–associated herpesvirus infection among Han and Uygur populations in Xinjiang, China

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