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Journal of Clinical Microbiology, June 1998, p. 1784-1786, Vol. 36, No. 6
Institute for Medical Microbiology,
Received 17 December 1997/Returned for modification 24 February
1998/Accepted 24 March 1998
The seroprevalence of human herpesvirus 8 (HHV-8) in the Swiss
population was investigated. By enzyme-linked immunosorbent assay, sera
reactive to the recombinant HHV-8 antigen orf 65.2 were found in 24%
of human immunodeficiency virus (HIV)-positive patients without and in
92% of HIV-positive patients with Kaposi's sarcoma. Surprisingly,
20% of homosexual HIV-negative men, versus only 7% of heterosexual
HIV-negative individuals and 5% of blood donors, had antibodies to
HHV-8.
In 1994, Chang et al. (7)
identified DNA fragments of a novel herpesvirus in Kaposi's sarcoma
(KS) tissue samples. This newly discovered virus was termed Kaposi's
sarcoma-associated herpesvirus or human herpesvirus 8 (HHV-8). By PCR
techniques, HHV-8 was found in more than 90% of human immunodeficiency
virus (HIV)-associated KS lesions, classic KS, and
posttransplant-associated KS (1, 5, 9, 13, 17, 20), as well
as in two lymphoproliferative disorders, body cavity-based lymphoma and
multicentric Castleman's disease (6, 23). Serological data
obtained from immunoblotting and immunofluorescence studies link the
distribution of HHV-8 with the risk of developing KS (11, 14, 15,
18, 22). In Western countries, a considerably higher
seroprevalence of HHV-8 (ranging from 13 to 35%) was found in
HIV-infected male homosexuals than in blood donors (0 to 8%). An
increased seroprevalence was also reported from areas with
endemic KS, such as central and eastern Africa and Mediterranean
countries (12, 15, 21). Recently, three groups
developed enzyme-linked immunosorbent assays (ELISAs) using
selected HHV-8-encoded proteins with low sequence homologies to corresponding Epstein-Barr virus (EBV)
proteins (2, 8, 21). However, the seroprevalence results
obtained varied considerably. This may have been due to regional
population differences, although different sensitivity levels of the
tests or possible cross-reactivities to other herpesviruses, which have not been excluded, seem more likely. By the sensitive ELISA to the
HHV-8 orf 65.2 protein (21), seroprevalence rates in various Swiss population groups were investigated.
A total of 571 sera from 113 HIV-positive and 458 HIV-negative
individuals were analyzed. The HIV-infected group included 26 sera from
patients with KS, 21 sera from asymptomatic (Centers for Disease
Control and Prevention [CDC] stage A) subjects, and 66 sera from
symptomatic (CDC stage B or C) patients. All patients were participants
in the Swiss HIV Cohort Study. The HIV-negative group included 123 sera
from individuals with various known herpesvirus infections, 35 sera
from patients with lymphoproliferative diseases, 122 sera from
individuals visiting an AIDS counseling center, of whom 54 were
homosexual or bisexual men and 68 were heterosexual men or women, and
178 sera from blood donors. ELISAs were performed with, as antigen,
recombinant orf 65.2 proteins expressed in M14 bacteria and purified by
affinity chromatography on Ni-nitrilotriacetic acid resin (Qiagen,
Basel, Switzerland), as described elsewhere (21). Sera were
diluted 1:80 in phosphate-buffered saline containing 0.1% Tween 20 for
cross-reactivity and 1:100 for seroprevalence studies. Cutoff values
were calculated from blood donor sera as the mean plus 5 standard
deviations. To adjust for interassay variability, the same five
negative blood donor sera were used to determine the cutoff for each
plate. Two reactive sera from patients with KS were included per plate
as positive controls. All sera were blindly tested and reactive sera or
sera with values close to the cut-off were retested at least once. For
confirmation, indirect immunofluorescence assays (IFAs) for antibodies
to latent HHV-8 antigens were done with, as target, the BC-3 cell line, as described elsewhere (3). A serum dilution of 1:40 was
used and all slides were evaluated by two independent examiners.
Immunoglobulin G antibodies to herpes simplex virus (HSV),
cytomegalovirus (CMV), varicella-zoster virus (VZV), EBV, and HHV-6
were measured with commercial ELISAs and IFAs. Prevalence results among
different patient groups were compared with the chi-square test.
Table 1 shows good concordance of
antibody reactivity to orf 65.2, as measured by ELISA, and to latent
antigen, as determined by IFA. For patients with KS, 92 and 88% of the
sera were reactive in ELISA and IFA, respectively, with both assays
together yielding 100% reactivity. For a control group of 35 patients
with lymphoproliferative diseases, only two and one sera were reactive
in ELISA and IFA, respectively. Our ELISA results are similar to those
of Simpson et al. (21), who reported a seroprevalence of
84% among KS patients with the same assay. Other groups found
prevalence rates ranging from 67 to 100% among patients with KS by
using IFA or immunoblots (12, 14, 16, 22), while in ELISAs
to HHV-8 orf 26 and orf 35, only 35 (2) and 60%
(8), respectively, of the KS sera were reactive. Thus, the
ELISA to orf 65.2 demonstrates good sensitivity, making the assay an
excellent tool for seroepidemiological studies.
However, as pointed out by Rickinson (19), a major concern
for seroepidemiological investigations with HHV-8 is possible antibody
cross-reactivity between HHV-8 and antigens of other herpesviruses.
Thus, 123 sera which had antibodies against at least one member of the
herpesvirus group were tested for possible cross-reactivity with the
HHV-8 orf 65.2 antigen. Thirteen sera (11%) were reactive to HHV-8 in
the ELISA. The prevalence of antibodies to HHV-8 was similar in the HSV
(5 of 31 [16%]), VZV (9 of 51 [18%]), CMV (3 of 19 [16%]), EBV
(4 of 31 [13%]), and HHV-6 (3 of 18 [17%]) seropositive
subgroups. In addition, three sera with very high antibody titers to
other herpesviruses were negative for HHV-8 and three sera highly
positive for HHV-8 were negative for all other herpesviruses studied.
Thus, the orf 65.2 ELISA specifically detects antibodies to HHV-8, with
no cross-reactivity to antibodies against the other members of the
herpesvirus family.
HHV-8 seroprevalence was investigated in different HIV-positive and
-negative groups. For HIV-positive patients with KS, 92% of the sera
had antibodies to orf 65.2 versus 24% (21 of 87) in individuals
without KS (Table 2), a prevalence rate
comparable to published data ranging from 13 to 35% (8, 11, 12,
14, 16, 21, 22). There was neither a correlation of HHV-8
seropositivity with HIV disease stages
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
High Human Herpesvirus 8 Seroprevalence in the
Homosexual Population in Switzerland
ABSTRACT
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TABLE 1.
Comparison of antibody reactivities to orf 65.2 protein
(determined by ELISA) and to latent HHV-8
antigens (determined by IFA)
as patients with CDC stage A (5 of 21 [24%]) or stages B and C (16 of 66 [24%]) of HIV disease
had the same seroprevalencenor with CD4 counts (data not shown), as
also found by two other studies (8, 21). Among the
HIV-infected patients without KS, homosexuals had a higher prevalence
of antibodies (30%) than did heterosexuals (25%) and intravenous drug
users (0%), although the patient numbers tested were small in the two latter groups (Table 2). This is in agreement with various studies (8, 11, 12, 14, 16, 22) with the exception of that of
Lennette et al. (15), who found HHV-8-reactive sera in
nearly all American HIV-infected homosexual men tested.
TABLE 2.
Seroprevalence of antibodies against HHV-8 orf 65.2 among
HIV-infected and uninfected individualsa
Except in certain KS-endemic regions of southern Europe, the rate of infection with HHV-8 in the general population in Western countries is low (11, 12, 14, 21). In agreement with this observation, we found an HHV-8 prevalence of 7% in the heterosexual population (persons attending an AIDS counseling center) and of 5% in blood donors but a somewhat higher seroprevalence (13 to 18%) in individuals with known herpesvirus infections. This may reflect a higher rate of infection with HHV-8 in a population already infected with other herpesviruses and/or the presence of homosexuals in this population (see below). The seroprevalence in the HIV-negative population tended to increase with age (Table 3) but was almost identical between men and women (7 of 133 [5%] and 2 of 45 [4%], respectively, in blood donors and 3 of 33 [9%] and 2 of 35 [6%], respectively, in the heterosexual population). Of considerable interest, and in contrast to Simpson et al. (21), we found a significantly higher seroprevalence in HIV-negative homosexual men than in heterosexuals (20 versus 7% [Table 2]). The high rate of infection with HHV-8 in homosexuals and the fact that HIV-infected individuals who develop KS are mostly homosexuals strongly indicates that perhaps one important mode of transmission of HHV-8 is through homosexual practices. This view is supported by observations that the prevalence of sporadic cases of KS is increased in HIV-negative homosexuals (10) and that women who have sexual contacts with HIV-infected bisexual men are more likely to develop KS than women whose sexual partners are HIV-infected intravenous drug users (4).
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ACKNOWLEDGMENTS |
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We thank G. Simpson for providing the orf 65.2 plasmid in M14 bacteria; E. Cesarman for providing the BC-3 cell line; Marc Bedoucha, Denise Bienz, Kurt Bienz and the staff of the serology laboratory of the Institute for Medical Microbiology for technical assistance; Sybille Stauffer and Elsbeth Baumgartner for immunofluorescence evaluations; and Peter Gowland for reading the manuscript.
This work was supported by grant 3139-046014.95 from the Swiss National Science Foundation.
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FOOTNOTES |
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* Corresponding author. Mailing address: Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland. Phone: (41) 61 267 32 75. Fax: (41) 61 267 32 98. E-mail: erb{at}ubaclu.unibas.ch.
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Journal of Clinical Microbiology, June 1998, p. 1784-1786, Vol. 36, No. 6
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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