Human Herpesvirus‐8 Infection and Oral Shedding in Amerindian and Non‐Amerindian Populations in the Brazilian Amazon Region

Laboratory of Virology, São Paulo Institute of Tropical Medicine and Department of Infectious and Parasitic Diseases, School of Medicine, University of São Paulo, São Paulo, Brasil.
The Journal of Infectious Diseases (Impact Factor: 6). 09/2007; 196(6):844-52. DOI: 10.1086/520549
Source: PubMed


Human herpesvirus type 8 (HHV-8) is hyperendemic in Amerindian populations, but its modes of transmission are unknown.
Antibodies against either HHV-8 lytic antigen or HHV-8 latency-associated nuclear antigen (LANA) were detected, by immunofluorescence assays, in 339 Amerindians and 181 non-Amerindians from the Brazilian Amazon. Serological markers of oro-fecal (hepatitis A), parenteral (hepatitis B and C), and sexual (herpes simplex virus type 2 and syphilis) transmission were measured by specific ELISAs. Salivary HHV-8 DNA was detected by use of a nested polymerase chain reaction assay and was sequenced.
Antibodies against either lytic antigen or LANA were detected in 79.1% of Amerindians and in 6.1% of non-Amerindians (adjusted seroprevalence ratio [SR], 12.63 [95% confidence interval {CI}, 7.1-22.4]; P<.0001). HHV-8 seroprevalence increased with age among Amerindians (P(Trend) < .001) and already had high prevalence in childhood but was not sex specific in either population. The 2 populations did not differ in seroprevalence of oro-fecal or parenteral markers, but seroprevalence of markers of sexual transmission was lower among Amerindians. HHV-8 DNA in saliva was detected in 47 (23.7%) of 198 HHV-8 seropositive Amerindians. Detection of HHV-8 DNA decreased with age (P(Trend) < .04) and was more common in men (SR, 2.14 [95% CI, 1.3-3.5]; P=.003). A total of 36 (76.6%) of the 47 saliva HHV-8 DNA samples were sequenced, and all clustered as subtype E.
The data support the hypothesis of early acquisition and horizontal transmission, via saliva, of HHV-8 subtype E in Amerindian populations.

Download full-text


Available from: Laura Masami Sumita, Aug 06, 2015
  • Source
    • "It is still unclear whether different viral variants may have different pathogenic and tumorigenic properties associated with a diverse rate of disease progression (Whitby et al., 2004; Mancuso et al., 2008). Notably, HHV-8 has been found hyperendemic among Amerindians tribes, with seroprevalence >80% in adults, despite the apparently low KS incidence (Mohanna et al., 2005; de Souza et al., 2007), suggesting that viral characteristics, environmental and/or host genetic factors are responsible for the low risk of cancer progression. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Kaposi's sarcoma (KS) is a rare cancer in Iran and there is no epidemiological and molecular information about HHV-8 variants circulating among the Iranian population. In this study HHV-8 sequences have been analyzed in 43 cutaneous KS biopsies from Iranian patients mainly affected by classic KS. DNA samples were subjected to PCR amplification of HHV-8 ORF26, T0.7 and K1 followed by direct nucleotide sequencing and phylogenetic analysis. The analysis of ORF26 showed that 30 (69.8%) and 13 (30.2%) samples belonged to subtypes A/C and K, respectively. In general, the clustering of HHV-8 T0.7 variants paralleled that of ORF26. Genotyping of K1 sequences showed that the majority of samples (39 out of 41) fall into the large C clade with only 2 belonging to the A clade. In conclusion, HHV-8 variants identified among classic Iranian KS are largely related to Eurasian genotypes previously identified in KS from Mediterranean, Middle East, and East Asian regions.
    Virus Research 09/2011; 163(2):644-9. DOI:10.1016/j.virusres.2011.09.027 · 2.32 Impact Factor
  • Source
    • "Of note, saliva represented the second most frequent source for HHV-8 detection (Figure 1). In the light of previous reports [11-13] and consistent with the present results transmission by saliva may contribute to the spread of HHV-8 infection among the HIV seropositive population besides sexual intercourse [14]. It still remains controversial why, if saliva is the main source of virus, HHV-8 infection shows a sexual pattern of transmission. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In Cuba, previous reports have shown an increase of epidemic KS, reaching a total of 120 cases by the end of 2007, despite the use of HAART. To evaluate and compare the role of human herpes virus 8 (HHV-8) viral loads in different compartments of AIDS-related Kaposi's sarcoma (AIDS-KS) patients real-time polymerase chain reaction (RT-PCR) was used to determine the genome copy number of HHV-8 in plasma, saliva, tissue and peripheral blood mononuclear cells (PBMC) of 49 AIDS-KS patients. Overall, 98% of AIDS-KS patients harbored detectable HHV-8. HHV-8 could be detected in 91.6% of KS tissue lesions showing the highest viral load (median log = 3.14 copies/100 ng DNA) followed by saliva and PBMC which were positive in 78%, and 69.2%; respectively. In contrast, HHV-8 was detected in only 37% of plasma samples, which also showed lower viral loads. Men who had sex with men (MSM) were more likely to have three-times higher HHV-8 genome copies in KS lesions when compared with tissues from heterosexuals individuals (OR 3; 95% CI 1.1 to 12.5). These results emphasize the systemic nature of HHV-8-infection and demonstrate the possible role of saliva in HHV-8 transmission among MSM.
    12/2010; 1(1):3. DOI:10.1186/2042-4280-1-3
  • Source
    • "Our previous work showed that the activation of KSHV lytic gene expression occurs during keratinocyte differentiation in an in vitro model of oral epithelium (Johnson et al., 2005) providing possible rationale for the oral cavity being the anatomic site with the highest levels of KSHV (Al-Otaibi et al., 2009; Ambroziak et al., 1995; Blackbourn et al., 1998; de Souza et al., 2007; Duus et al., 2004; Gasperini et al., 2005; Koelle et al., 1997; LaDuca et al., 1998; Vieira et al., 1997). In this work, we have used additional models of keratinocyte differentiation to begin an investigation of the early aspects of keratinocyte differentiation that control KSHV reactivation and have identified the following: (1) the movement of keratinocytes into the first suprabasal layer is the point of KSHV lytic activation; (2) engagement of integrins with their ligands inhibits KSHV reactivation; (3) cell–cell contact, necessary for the formation of adherens junctions by cadherins, is not required for reactivation; (4) increased levels of intracellular and extracellular calcium and the initiation of differentiation are not sufficient for KSHV reactivation in cells attached to a substratum; however, extracellular calcium is necessary in cells that have loss substratum contact; and (5) KSHV lytic activation can occur prior to late differentiation. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously found that KSHV (HHV-8) lytic activation occurs during differentiation of oral keratinocytes in organotypic raft cultures. To further investigate the spatial and temporal aspects of KSHV lytic activation and the roles of integrins, cadherins, and calcium, we used rKSHV.219-infected primary oral keratinocytes in submerged, suspension, and direct suprabasal plating, models of differentiation. We found that early keratinocyte differentiation did not activate lytic KSHV in cells attached to a substratum, with activation only occurring in suprabasal cells. Temporally, KSHV lytic expression occurred between the expression of early and late differentiation markers. Keratinocytes differentiated in suspension culture, which mimics substratum loss that occurs with stratification, activated lytic KSHV. This lytic activation was inhibited by integrin engagement, showing that integrins are a control point for KSHV reactivation. A role for cadherins was not found. Elevated extracellular calcium was necessary, but not sufficient, for lytic activation.
    Virology 11/2010; 410(1):17-29. DOI:10.1016/j.virol.2010.10.023 · 3.32 Impact Factor
Show more