BACKGROUND: As part of assessing the possibility of transfusion transmission of human herpesvirus 8 (HHV‐8 or Kaposi's sarcoma‐associated herpesvirus), HHV‐8 seroprevalence was estimated among US ...blood donors, the performance of HHV‐8 serologic tests was compared, and the presence of HHV‐8 DNA was tested for in donated blood.
STUDY DESIGN AND METHODS: Replicate panels of 1040 plasma specimens prepared from 1000 US blood donors (collected in 1994 and 1995) and 21 Kaposi's sarcoma patients were tested for antibodies to HHV‐8 in six laboratories. HHV‐8 PCR was performed on blood samples from 138 donors, including all 33 who tested seropositive in at least two laboratories and 22 who tested positive in at least one.
RESULTS: The estimated HHV‐8 seroprevalence among US blood donors was 3.5 percent (95% CI, 1.2%‐9.8%) by a conditional dependence latent‐class model, 3.0 percent (95% CI, 2.0%‐4.6%) by a conditional independence latent‐class model, and 3.3 percent (95% CI, 2.3%‐4.6%) by use of a consensus‐derived gold standard (specimens positive in two or more laboratories); the conditional dependence model best fit the data. In this model, laboratory specificities ranged from 96.6 to 100 percent. Sensitivities ranged widely, but with overlapping 95 percent CIs. HHV‐8 DNA was detected in blood from none of 138 donors evaluated.
CONCLUSIONS: Medical and behavioral screening does not eliminate HHV‐8‐seropositive persons from the US blood donor pool, but no viral DNA was found in donor blood. Further studies of much larger numbers of seropositive individuals will be required to more completely assess the rate of viremia and possibility of HHV‐8 transfusion transmission. Current data do not indicate a need to screen US blood donors for HHV‐8.
Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic.
We ...enrolled patients in Kampala, Uganda, who had received blood transfusions between December 2000 and October 2001. Pretransfusion and multiple post-transfusion blood specimens from up to nine visits over a 6-month period were tested for HHV-8 antibody. We calculated the excess risk of seroconversion over time among recipients of HHV-8-seropositive blood as compared with recipients of seronegative blood.
Of the 1811 transfusion recipients enrolled, 991 were HHV-8-seronegative before transfusion and completed the requisite follow-up, 43% of whom received HHV-8-seropositive blood and 57% of whom received seronegative blood. HHV-8 seroconversion occurred in 41 of the 991 recipients. The risk of seroconversion was significantly higher among recipients of HHV-8-seropositive blood than among recipients of seronegative blood (excess risk, 2.8%; P<0.05), and the increase in risk was seen mainly among patients in whom seroconversion occurred 3 to 10 weeks after transfusion (excess risk, 2.7%; P=0.005), a result consistent with the transmission of the virus by transfusion. Blood units stored for up to 4 days were more often associated with seroconversion than those stored for more than 4 days (excess risk, 4.2%; P<0.05).
This study provides strong evidence that HHV-8 is transmitted by blood transfusion. The risk may be diminished as the period of blood storage increases.
Human herpesvirus 8 (HHV-8), the causal agent of Kaposi's sarcoma, is transmitted sexually among homosexual men, but little is known of its transmission among women. Although HHV-8 has been detected ...in blood, there has been no clear evidence of blood-borne transmission.
We identified risk factors for HHV-8 infection in 1295 women in Baltimore, Detroit, New York, and Providence, Rhode Island, who reported high-risk sexual behavior or drug use. HHV-8 serologic studies were performed with two enzyme-linked immunosorbent assays.
In univariate analyses, HHV-8 was associated with black race, Hispanic ethnic background, a lower level of education, and infection with syphilis, the human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). The risk of seropositivity for HHV-8 increased with the frequency of injection-drug use (P<0.001); HHV-8 seroprevalence among the women who used drugs daily was three times that among women who never injected drugs. Among the women with a low risk of sexual transmission, HHV-8 seroprevalence was 0 percent in those who had never injected drugs and 36 percent in those who had injected drugs (P<0.001). However, injection-drug use was linked less strongly to HHV-8 infection than to infection with HBV or HCV. In a multivariate analysis, independent predictors of HHV-8 seropositivity included HIV infection (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.2), syphilis infection (odds ratio, 1.8; 95 percent confidence interval, 1.1 to 2.8), and daily injection-drug use (odds ratio, 3.2; 95 percent confidence interval, 1.4 to 7.6).
Both injection-drug use and correlates of sexual activity were risk factors for HHV-8 infection in the women studied. The independent association of HHV-8 infection with injection-drug use suggests that HHV-8 is transmitted through needle sharing, albeit less efficiently than HBV, HCV, or HIV.
Detection of novel DNA sequences in Kaposi's sarcoma (KS) and AIDS-related body cavity-based, non-Hodgkin's lymphomas suggests that these neoplasms are caused by a previously unidentified human ...herpesvirus. We have characterized this agent using a continuously infected B-lymphocyte cell line derived from an AIDS-related lymphoma and a genomic library made from a KS lesion. In this cell line, the agent has a large episomal genome with an electrophoretic mobility similar to that of 270-kb linear DNA markers during clamped homogeneous electric field gel electrophoresis. A 20.7-kb region of the genome has been completely sequenced, and within this region, 17 partial and complete open reading frames are present; all except one have sequence and positional homology to known gammaherpesvirus genes, including the major capsid protein and thymidine kinase genes. Phylogenetic analyses using both single genes and combined gene sets demonstrated that the agent is a gamma-2 herpesvirus (genus Rhadinovirus) and is the first member of this genus known to infect humans. Evidence for transient viral transmission from infected to uninfected cells is presented, but replication-competent virions have not been identified in infected cell lines, and these antibodies are generally absent in sera from patients with AIDS without KS. These studies define the agent as a new human herpesvirus provisionally assigned the descriptive name KS-associated herpesvirus; its formal designation is likely to be human herpesvirus 8.
Abstract The human cytomegalovirus (HCMV) US12 gene family is a group of 10 predicted seven-transmembrane domain proteins that have some features in common with G-protein-coupled receptors. Little is ...known of their patterns of expression, localization, or functional interactions. Here, we studied the intracellular localization of three US12 family members, US14, US17, and US18, with respect to various intracellular markers and the cytoplasmic virion assembly compartment (AC). The three proteins have distinct patterns of expression, which include associations with the AC. US14 is often distributed in a uniform granular manner throughout the cytoplasm, concentrating in the AC in some cells. US17 is expressed in a segmented manner, with its N-terminal domain localizing to the periphery of what we show here to be the AC and the C-terminal domain localizing to nuclei and the cytoplasm Das, S., Skomorovska-Prokvolit, Y., Wang, F. Z., Pellett, P.E., 2006. Infection-dependent nuclear localization of US17, a member of the US12 family of human cytomegalovirus-encoded seven-transmembrane proteins. J. Virol. 80, 1191–1203. Here, we show that the C-terminal domain is present at the center of the AC, in close association with markers of early endosomes; the N-terminal staining corresponds to an area stained by markers for the Golgi and trans-Golgi. US18 is distributed throughout the cytoplasm, concentrating in the AC at later stages of infection; it is localized more to the periphery of the AC than are US14 and US17C, in association with markers of the trans-Golgi. Although not detected in virions, their structures and localization in various zones within the AC suggest possible roles for these proteins in the process of virion maturation and egress.
PDF
