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First report of Kaposi's sarcoma-associated herpesvirus DNA sequences from Cuban Kaposi's sarcoma patients without HIV infection

Kourí, Viviana; Martínez, Pedro Aa; Acosta, Belsya; Rodríguez, María Ea; Blanco, Orestesa; Capó, Virginiaa; González, Ruby La; Viera, Jenniffera; Hengge, Ulrich Rb

doi: 10.1097/QAD.0b013e3282f01cc6

aInstituto de Medicina Tropical ‘Pedro Kouri’, Ciudad de La Habana, Cuba

bDepartment of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.

Received 7 May, 2007

Revised 15 May, 2007

Accepted 22 May, 2007

Classic Kaposi's sarcoma (KS) most often occurs in Europe and north America in elderly men of Italian or eastern European Jewish descent [1]. Moreover, this neoplasm may also be detected in several other distinct populations such as young black African men, prepubescent children, renal allograft recipients, and in homosexual HIV-negative men [1].

We report, for the first time, four Cuban KS patients without HIV infection and provide data on the molecular epidemiology of their virus.

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Case 1 (Cu44-06)

A 61-year-old white heterosexual man reported a maculopapular purple tumour on the plantar region of his right foot with accompanying lymph oedema, which made walking painful. He was married and denied any homosexual contacts. He had been travelling to Angola between 1993 and 1995. His CD4 cell count was 1058 cells/μl. Quantitative real-time polymerase chain reaction (PCR) of DNA extracted from the histologically confirmed KS lesion and his peripheral blood mononuclear cells (PBMC) was performed as recently described [2,3], and came out positive showing a viral load of 8818 and 245 copies/106 cells, respectively (Table 1).

The ORFK1 gene was amplified from the genomic DNA extracted from the skin lesions using the primers 2089/2088 (1063 base pairs; bp), which covered the complete 870 bp K1 coding region and for the nested PCR reaction the internal primers 2090/2508, which amplify a fragment of 621 bp (nucleotides 117–738) as previously described [4]. Sequence analysis of the ORFK1 gene revealed the presence of Kaposi's sarcoma-associated herpesvirus (KSHV) subtype A2.

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Case 2 (Cu-B636/06)

A 39-year-old white homosexual man complained of the appearance of an indolent 5 mm lesion on his right lower knee. The patient had a previous history of sexual intercourse with an HIV-infected individual, although he reported strict protection using condoms. He had not travelled abroad. He had been tested negative for HIV-1 and HIV-2 several times and his CD4 cell count was 783 cells/μl. Real-time PCR analysis of the KS lesion, PBMC and saliva revealed 20000, 7833 and 12 550 KSHV copies/106 cells, respectively (Table 1). The virus was sequenced to belong to KSHV subtype B.

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Case 3 (Cu-683/06)

A 58-year-old white heterosexual man, who had worked as a medical doctor in Mozambique from 1978 to 1980, while he maintained an unprotected sexual relationship with a native woman, denied any homosexual relationships. In 2000 and 2006, the patient noticed purple lesions on his left heel that were histologically diagnosed as KS, which contained a high KS viral load of 484 000, 1358 and 233 000 copies/106 cells, respectively (Table 1). The virus belonged to KSHV subtype B.

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Case 4 (Cu-729/06)

A 64-year-old white, divorced female gynaecologist presented with maculopapular lesions on her right forearm, the right hand, and two other small lesions on the left arm. The histological diagnosis of two different lesions confirmed KS. She has never travelled abroad and reported not having had sex since 1984. Her HIV test was negative. The KSHV load from affected skin yielded 190 copies/106 cells (Table 1) and belonged to the rare subtype E.

Classic KS occurs with a ratio of approximately 10–15 men to one woman at older age. It presents as one or more asymptomatic red, purple, or brown patches, plaques, or less frequently as nodular skin lesions on the lower extremities, especially on the shins, the ankles and soles. Classic KS takes a relatively benign, indolent course for 10–15 years or more [1].

According to clinical-epidemiological criteria previously described elsewhere [1], patients 1, 3 and 4, were classified as having classic KS (Table 1). In contrast, case 2 should be classified as non-epidemic homosexual-related KS [5]. Given his report of practising safer sex with an HIV-infected man, other sources of KSHV transmission such as saliva should be considered in this case.

In agreement with our previous reports on KSHV subtypes among the Cuban HIV population [2–4], the current study indicates a wide variety of KSHV subtypes among the non-HIV Cuban population (see GenBank accession numbers below). No ethnic association has been found suggesting that KSHV has spread to the Caribbean and south America from different sources (Europe, Africa), whereas subtype E may have been endemic among the Aborigines, who in Cuba were almost completely eradicated after colonization. Therefore, we assume that subtypes A and C were introduced to Cuba from Hispanic immigrants, whereas subtypes B and A5 may have been introduced by Africans. Despite this, we cannot discard the hypothesis of the more recent introduction of KSHV from Cuban individuals who were working in Africa during the 1970s and 1980s.

The detection of higher KSHV loads was recently found to be associated with the development of classic KS [6]. Matched PBMC, saliva and tissue samples as in our case have not, however, been systematically analysed with regard to viral characteristics (e.g. viral load and genotype) in non-HIV KS individuals.

GenBank accession numbers of the new sequences: EF153263: Cu44-06; EF153264: Cu-729/06; EF153265: Cu-B636/06; EF153266: Cu-683/06.

Sponsorship: This work was supported by the Joachim-Kuhlmann AIDS Foundation, grant no. 2347/06.

Conflicts of interest: None.

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