Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III, Majadahonda, Spain.
CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
PLoS One. 2022 Oct 25;17(10):e0274058. doi: 10.1371/journal.pone.0274058. eCollection 2022.
Since human herpesvirus 8 (HHV-8) infection may be underestimated and HHV-8 subtype circulation in Spain remains unknown, a molecular epidemiologic study is highly desirable.
This study aimed to analyse HHV-8 subtype diversity and their distribution in Spain.
The study included 142 HHV-8 infected patients. A nested PCR was developed in order to permit Sanger sequencing of HHV-8 K1 ORF directly from clinical samples received at the CNM from 2013 to 2021. Phylogenetic characterization was performed.
Genotypes A and C comprised 55.6% and 42.3% of strains. Regarding subtypes, 25.4% of strains were C3, 19.7% were A3, 14.1% were A5, and C2, A1, A4, C1, A2, C7 were 11.3%, 11.3%, 8.5%, 4.2%, 2.1% and 1.4%, respectively. Subtype E1, E2 and B1 were found in only one patient each (0.7%). The Madrid region accounted for 52.1% of patients and showed a significantly different subtype distribution compared to the others (P = 0.018). Subtypes B1, E1, and E2 were observed to appear sporadically, although overall genotypes A and subtype C3 remained the most frequent and unwavering. Subtype A3 presented the highest diversity as displayed by the highest number of clusters in phylogenetic analysis. Non-significant differences in viral loads between genotypes were found, but significantly higher viral loads in subtype C2 compared to subtype C3 was found, while no significant subtype differences were observed between subtypes within genotype A. Infections with HHV-8 were detected in 94 (66.2%) patients without KS and compared to patients with KS non-significant differences in subtype distribution were found.
Subtype prevalence and regional distribution followed a similar pattern compared to other western European countries. Our study is the first to report HHV-8 subtypes E1 and E2 circulating in Europe that might be reflective of migration of population from Caribbean countries. Our study suggests that infection by HHV-8 is underestimated, and wider screening should be recommended for risk groups.
由于人类疱疹病毒 8 型(HHV-8)感染可能被低估,且 HHV-8 亚型在西班牙的流行情况尚不清楚,因此非常需要进行分子流行病学研究。
本研究旨在分析西班牙 HHV-8 亚型的多样性及其分布。
本研究纳入了 142 例 HHV-8 感染患者。我们开发了巢式 PCR 方法,以便能够直接从 2013 年至 2021 年在 CNM 收到的临床样本中对 HHV-8 K1 ORF 进行 Sanger 测序。我们进行了系统发育特征分析。
基因型 A 和 C 分别占 55.6%和 42.3%的菌株。关于亚型,25.4%的菌株为 C3,19.7%为 A3,14.1%为 A5,C2、A1、A4、C1、A2、C7 分别为 11.3%、11.3%、8.5%、4.2%、2.1%和 1.4%。每个患者各发现了 1 例亚型 E1、E2 和 B1(0.7%)。马德里地区占患者的 52.1%,与其他地区相比,其亚型分布存在显著差异(P = 0.018)。尽管总体上基因型 A 和亚型 C3 仍然是最常见且稳定的,但我们发现 B1、E1 和 E2 亚型的出现较为零星。在系统发育分析中,A3 亚型表现出最高的多样性,聚类数量最多。基因型之间的病毒载量无显著差异,但与 C3 亚型相比,C2 亚型的病毒载量显著更高,而在 A 基因型内的亚型之间未观察到显著的亚型差异。在 94 例(66.2%)无卡波西肉瘤的患者中检测到 HHV-8 感染,与卡波西肉瘤患者相比,其亚型分布无显著差异。
与其他西欧国家相比,本研究中西班牙 HHV-8 亚型的流行情况和地区分布模式相似。本研究首次报道了在欧洲流行的 HHV-8 亚型 E1 和 E2,这可能反映了来自加勒比国家的人口迁移。我们的研究表明,HHV-8 感染被低估了,应该建议对高危人群进行更广泛的筛查。