Human herpesvirus 8 in semen and prostate

The prevalence of human herpesvirus (HHV) type 8 determined by polymerase chain reaction (PCR) in specimens from various individuals has been described in a number of reports. Interpreting these data can be difficult, however, because of the inherent sensitivity of the PCR method, which renders such diagnostic assays susceptible to artefacts and to the possibility that the amplification signal is derived from infiltrating cells which are themselves infected by the virus. In this regard, two reports in this issue of AIDS [1,2] counter previous findings from molecular studies on the prevalence of HHV-8 in seminal fluids and prostate glands in the HIV-negative human population (Table 1). Two important issues arise in concluding whether HHV-8 is commonly found in these specimens. First, is the HHV-8 infection prevalent in a substantial proportion of the healthy human population? Second, is a sexual route for transmission of HHV-8 substantiated?Table 1: . Prevalence of human herpesvirus 8 by polymerase chain reaction (PCR) analyses in semen and prostate glands.Howard et al. [1] in their study of 115 semen donors to a fertility clinic in London, challenge a provocative earlier study by Monini et al. [3] who detected HHV-8 in 91% of semen specimens from HIV-negative Italian donors. Such widespread prevalence of HHV-8 in the HIV-negative population has not been substantiated even by the most sensitive serologic techniques [4]. The men evaluated in the study by Monini et al. [3] may not be representative of the healthy population, however. The semen donations came from healthy Italian individuals but they had varioceles. Could this male population be biased? It seems unlikely, but demographic or geographic differences may have influenced the results. HHV-8 infection might be more common in some men from certain regions of Italy than England. Indeed, the rate of detection of HHV-8 in the semen of healthy men (23%) noted by Lin et al. [5] and in a more recent study of Italian men by Monini et al. [6] mirrors the HHV-8 seroprevalence (25%) reported for the healthy population [4]. Whether the virus exists in healthy individuals at a high frequency, however, still remains controversial. Nevertheless, the consensus from the literature does indicate that the virus is present in the semen of HIV-infected men (Table 1). The data certainly imply a sexual route of transmission. As for the prostate gland, the findings of Lebbé et al. [2] are consistent with those others (Table 1), who suggest that HHV-8 is not associated with this site in HIV-negative individuals. In contrast, Monini et al. [3,6] have detected HHV-8 in normal, hyperplastic and neoplastic prostate glands of HIV-negative individuals. Nevertheless, infected infiltrating lymphocytes [7] could also provide the source of the PCR-positive signal. An appropriate control in such studies would be the examination for HHV-8 infection of peripheral blood cells and other tissues from the same subjects used for the prostate gland analyses. In this regard, Corbellino et al. [8] found HHV-8 infection predominantly restricted to the Kaposi's sarcoma (KS) lesions, prostate gland and lymphoid tissue in their non-nested PCR analyses of AIDS patients with KS. Most other organs evaluated were negative. Certainly, whether the prostate is the site of HHV-8 infection in either HIV-infected or uninfected men requires further evaluation with appropriate controls. Moreover, whether the neoplastic prostate is the site of HHV-8 infection and transformation, thereby implicating the virus in prostatic carcinoma, has yet to be verified. If the virus is present in the prostate of healthy individuals, or even those with KS, useful additional data would be whether those individuals with HHV-8-infected prostate glands shed detectable virus in the semen. In both controversies, whether the viral load is sufficiently high for HHV-8 to be involved either in sexual transmission via infected semen or in prostatic carcinoma is an important issue. Several studies have used a nested PCR procedure to detect HHV-8 in semen and prostate tissue (Table 1). Nested PCR is not needed to demonstrate the presence of the virus in either of the pathologic conditions with which HHV-8 is most strongly associated: KS or body cavity-based lymphomas. In summary, the prevalence of HHV-8 in the healthy human population remains unresolved, in part due to demographic and geographic differences but also perhaps the experimental approach in which PCR artefacts can confound the results. Hopefully, the HHV-8 serologic studies recently described [4,9–11] will provide reproducible and rapid assays for HHV-8 detection. Then, more reliable studies of the prevalence of this virus will be possible using a combination of molecular and serologic assays. An exchange among laboratories of specimens from different parts of the world would also facilitate the evaluation of the prevalence of HHV-8 in different tissues and body fluids. Such approaches should help to dispel much of the cynicism concerning past and perhaps future reports on HHV-8 prevalence in which PCR results alone are the only criteria. Thus far, however, the epidemiologic and serologic studies do suggest a sexual route of HHV-8 transmission. If not by semen, then by what? Acknowledgements The authors would like to thank D. Mourich and E. Barker for critical reading of this manuscript, and A. Murai for help in its preparation.