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T F Schulz

Publications and source records attributed to T F Schulz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Human herpes virus 8 infection in kidney transplant patients in Belgium.

BACKGROUND: Kaposi sarcoma (KS) may arise as a complication of kidney transplantation. In the Saint Luc Teaching Hospital in Brussels, patients of both Belgian and foreign origin are treated. The prevalence of human herpes virus 8 (HHV-8) infection differs in different geographical settings. We wanted to estimate the background infection rate and the risk of infection in our transplant population: a first step towards evaluating the necessity of HHV-8 screening. METHODS: Serum samples were taken from 210 organ donors over a period of 7 years (30 per year) and from 200 kidney recipients from whom two sera were tested, one pre-transplant and the second 6-12 months post-transplant. All sera were screened for HHV-8 by an enzyme-linked immunosorbant assay using recombinant ORF 65 and ORF 73 antigens and an immunofluorescence assay for the latent antigen. Reactive samples were confirmed by western blotting. RESULTS: Seven donors (3.3%) were positive for HHV-8 antibodies. Of 198 pre-transplant sera available for evaluation, 15 were positive (7.6%). Post-transplantation 18/199 (9%) were positive: four (2.1% of negatives) had a documented seroconversion and one lost the antibodies. No patients developed KS. CONCLUSIONS: A substantial number of kidney transplant patients already had antibodies to HHV-8 at the time of transplantation. A further 2.1% of seronegative patients had seroconversion, which could have been acquired through the transplanted organ (3.3% of donors were positive) or through transfusion.

Antibodies, Viral↗
PubMed2000

Two distinct gamma-2 herpesviruses in African green monkeys: a second gamma-2 herpesvirus lineage among old world primates?

Primate gamma-2 herpesviruses (rhadinoviruses) have so far been found in humans (Kaposi's sarcoma-associated herpesvirus [KSHV], also called human herpesvirus 8), macaques (Macaca spp.) (rhesus rhadinovirus [RRV] and retroperitoneal fibromatosis herpesvirus [RFHV]), squirrel monkeys (Saimiri sciureus) (herpesvirus saimiri), and spider monkeys (Ateles spp.) (herpesvirus ateles). Using serological screening and degenerate consensus primer PCR for the viral DNA polymerase gene, we have detected sequences from two distinct gamma-2 herpesviruses, termed Chlorocebus rhadinovirus 1 (ChRV1) and ChRV2, in African green monkeys. ChRV1 is more closely related to KSHV and RFHV, whereas ChRV2 is closest to RRV. Our findings suggest the existence of two distinct rhadinovirus lineages, represented by the KSHV/RFHV/ChRV1 group and the RRV/ChRV2 group, respectively, in at least two Old World monkey species. Antibodies to members of the RRV/ChRV2 lineage may cross-react in an immunofluorescence assay for early and late KSHV antigens.

Amino Acid Sequence↗
PubMed1999

Variability and evolution of Kaposi's sarcoma-associated herpesvirus in Europe and Africa. International Collaborative Group.

OBJECTIVE: To study the evolution of Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 in Europe and Africa. DESIGN AND METHODS: PCR and sequence analysis of the variable viral membrane glycoprotein gene K1 in 58 tumour and peripheral blood samples from patients with AIDS-related Kaposi's sarcoma (KS), 'classic' (HIV-negative) KS, transplant KS, Multicentric Castleman's Disease, other lymphoproliferative disorders, and healthy KSHV-infected individuals from the UK, Denmark, Sweden, Italy, Spain, Iceland, The Faroe Islands, Greece, The Gambia and Uganda. RESULTS: Three major groups of K1 sequences were found: A, B and C, as defined previously. The K1 gene has evolved, both within and between these three groups, under positive selection. KSHV group B strains predominate in Africa and are more distant from groups A and C, found in Europe, than A and C are from each other. Within group C two subgroups, C' and C", can be identified. Subgroup C" is more closely related to group A in a region of the K1 protein and appears to be phylogenetically close to the branchpoint between A and C. Group A and C strains are currently found in both HIV-1-infected and -uninfected Europeans, and were already present in Europe before the start of the AIDS epidemic. We found some examples of closely related K1 sequences in Italy and Denmark, but in general KSHV strains in Europe did not cluster geographically. CONCLUSION: KSHV strains in East and West Africa are closely related but phylogenetically distant from those in Europe. The two major KSHV groups in Europe are more closely related, with some strains adopting an intermediate phylogenetic position. In Europe, KSHV strains may have been disseminated at least several decades ago. Variability in the K1 region is driven by selection and does not correlate with different KSHV-related pathologies or geographic regions where clinically more aggressive HIV-negative KS ('endemic' KS) is more common.

AIDS-Related Opportunistic Infections↗
PubMed1999

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

Adult↗
PubMed1999

Human herpes-virus 8 seropositive patient with skin and graft Kaposi's sarcoma after lung transplantation.

Kaposi's sarcoma (KS) has been reported after solid organ transplantation mostly in recipients of renal, liver, heart, and bone allografts. We describe the first case of a patient with lung transplantation who developed KS of the skin, but also of the lung graft. The tumors were localized to places of previous trauma, implying the involvement of a Koebner phenomenon. Moreover, a polymerase chain reaction assay revealed the presence of DNA sequences of herpesvirus 8 (HHV-8) on tissue of the cutaneous KS. Serological tests showed HHV-8 seronegativity of the graft donor and HHV-8 seropositivity of the patient before lung transplantation suggesting that the latter was already infected before the surgery and that immunosuppression resulted in the development of KS. This case report raises the question of the prevalence of HHV-8 in candidates for transplantation and organ donors, and of the value of an antiviral prophylaxis to lower the risk of KS.

Herpesviridae Infections↗
PubMed1999

Kaposi's sarcoma-associated herpesvirus: a new human tumor virus, but how?

Kaposi's sarcoma-associated herpesvirus, or human herpesvirus 8, the most recently discovered human tumor virus, is involved in the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma and some cases of multicentric Castleman's disease. It is non-pathogenic in the majority of otherwise healthy individuals but highly oncogenic in the context of HIV-1 infection and iatrogenic immune suppression, and other cofactors might exist. Several viral genes can interfere with normal cell growth and differentiation, but their precise role in oncogenesis is still under investigation.

AIDS-Related Opportunistic Infections↗
PubMed1999

No evidence for a role of human herpesvirus type 8 in sarcoidosis: molecular and serological analysis.

The aim of this study was to analyse the association between human herpesvirus type 8 (HHV8) and sarcoidosis. Using nested polymerase chain reaction (PCR), we tested the presence of HHV8 DNA sequences in 13 skin specimens and peripheral blood mononuclear cells from eight patients suffering from sarcoidosis. We also looked for the presence of HHV8 antibodies in the sera of 28 patients with sarcoidosis using three techniques: two indirect immunofluorescence assays and an enzyme-linked immunosorbent assay with recombinant capsid protein fragment encoded by open-reading frame 65. HHV8 PCR analysis was negative while HHV8 serological studies showed an overall prevalence of 18% among patients suffering from sarcoidosis: 43% in patients from sub-Saharan Africa, 17% in patients from Northern Africa, 12.5% in patients from the French West Indies and 0% in French patients. In conclusion, our results do not indicate an association between HHV8 and sarcoidosis but reflect the seroepidemiology of this virus in different geographical regions.

Adult↗
PubMed1999

Human serum antibodies to a major defined epitope of human herpesvirus 8 small viral capsid antigen.

The major antibody-reactive epitope of the small viral capsid antigen (sVCA) of human herpesvirus 8 (HHV-8) was defined by use of overlapping peptides. Strong IgG reactivity was found among approximately 50% of 44 human immunodeficiency virus-positive or -negative patients with Kaposi's sarcoma and 13 subjects who were seropositive by immunofluorescence assay (IFA) for the latent HHV-8 nuclear antigen. Only 1 of 106 subjects seronegative for both lytic and latent HHV-8 antigens and 10 of 81 subjects IFA-seropositive only for the lytic HHV-8 antigen had strong IgG reactivity to this epitope. Among 534 healthy Swedish women, only 1.3% were strongly seropositive. Comparison of the peptide-based and purified sVCA protein-based ELISAs found 55% sensitivity and 98% specificity. However, only 1 of 452 serum samples from healthy women was positive in both tests. In conclusion, the defined sVCA epitope was a specific, but not very sensitive, serologic marker of active HHV-8 infection. Such infection appears to be rare among Swedish women, even with sexual risk-taking behavior.

Adolescent↗
PubMed1999

Detection of human herpesvirus 8 in cervicovaginal secretions and seroprevalence in human immunodeficiency virus type 1-seropositive and -seronegative women.

Epidemiologic studies suggest that human herpesvirus 8 (HHV-8) may be sexually transmitted. To study the potential for HHV-8 transmission through cervicovaginal (CV) secretions, the presence of HHV-8 DNA was investigated by nested polymerase chain reaction in the cellular fraction of CV secretions from 36 human immunodeficiency virus type 1 (HIV-1)-seropositive and 29 HIV-1-seronegative women. The same patients were tested for antibodies to two defined HHV-8 antigens (latency-associated nuclear antigen and open-reading frame 65-encoded structural protein) and for HHV-8 DNA in their peripheral blood mononuclear cells (PBMC). The findings were compared with the rate of HHV-8 detection in semen samples of 20 HIV-1-infected men. HHV-8 DNA was detected in the CV samples from only 1 HHV-8-seropositive AIDS patient, in 3 PBMC samples (1/29 HIV-1-seronegative patients, 1/3 AIDS patients with Kaposi's sarcoma, and 1/19 AIDS patients), and in 1 of 20 semen samples. HHV-8 infection was more common in HIV-1-infected than uninfected women. Thus HHV-8 DNA is only rarely detectable in CV secretions and semen of HHV-8-infected individuals.

Cervix Mucus↗
PubMed1999

Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers.

A survey of antibody responses to human herpesvirus 8 (HHV-8) was undertaken to examine the mode of transmission of this virus to children born to mothers with HIV. Methods. Serum samples from a cohort of 92 mother-infant pairs and a cross-sectional cohort of 100 children (median age, 4 years) were tested. In the cohort of mother-infant pairs, 14 infants were HIV-infected, 72 were not and the HIV status was unknown for 6. In the cohort of children 70 were HIV-infected and 30 were vertically exposed but uninfected. Serologic responses to two HHV-8 antigens, latency-associated nuclear antigen and the structural antigen encoded by open reading frame 65 were detected by immunofluorescent antibody test and enzyme-linked immunoassay. Results were confirmed by Western blot. Results. All HHV-8-seropositive mothers were African (17 of 92, 18.5%). Six of their infants were HHV-8-seronegative and 11 had at least 1 HHV-8-seropositive sample. One of the 11 infants tested only at birth had a lower antibody titer than the mother; the remaining 10 infants had decreasing titers up to 7 months of age and 6 became seronegative. No infants born to HHV-8-seronegative mothers had antibodies to the virus. The seroprevalence to HHV-8 was 6% in the cohort of children. All had African mothers and their median age was greater than that of the cohort (8.4 vs. 4.0 years). Five were coinfected with HIV. Conclusions. HHV-8 was not vertically transmitted by any of the HIV-coinfected mothers. Acquisition of antibody to HHV-8 occurred in older children, implying a horizontal route of transmission.

Adult↗
PubMed1999

Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene.

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is the likely infectious cause of Kaposi's sarcoma, primary effusion lymphoma, and some cases of multicentric Castleman's disease. Its latent nuclear antigen (LANA) is expressed in the nuclei of latently infected cells and may play a role in the persistence of episomal viral DNA in dividing cells. Here we report that LANA interacts with RING3, a nuclear protein and member of the Drosophila fsh (female sterile homeotic) family of proteins, some of which have previously been implicated in controlling gene expression. Binding of RING3 to LANA involves the ET domain, characteristic of fsh-related proteins, suggesting that this highly conserved region is involved in protein-protein interactions. The interaction between RING3 and LANA results in phosphorylation of serine and threonine residues located between amino acids 951 and 1107 in the carboxy-terminal region of LANA. However, RING3 is not itself a kinase but appears to recruit an as yet unidentified serine/threonine protein kinase into the complex which it forms with LANA.

Animals↗
PubMed1999

Identification of a spliced gene from Kaposi's sarcoma-associated herpesvirus encoding a protein with similarities to latent membrane proteins 1 and 2A of Epstein-Barr virus.

Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV-8) is a novel herpesvirus implicated as the causative agent of Kaposi's sarcoma (KS), primary effusion lymphoma, and some cases of multicentric Castleman's disease. KSHV persists in the majority of KS spindle (endothelial tumor) cells and lymphoid cells in a latent form, with only a limited set of viral genes expressed in a tissue-specific manner. Here, we report the identification of a family of alternatively-spliced transcripts of approximately 7.5 kb expressed in latently infected body cavity-based lymphoma (BCBL) cell lines which are predicted to encode membrane proteins with similarities to the LMP2A and LMP1 proteins of Epstein-Barr virus. In two highly divergent sequence variants of the right end of the KSHV genome, alternative splicing of eight exons located between KSHV ORF 75 and the terminal repeats yields transcripts appropriate for proteins with up to 12 transmembrane domains, followed by a hydrophilic C-terminal, presumably cytoplasmic, domain. This C-terminal domain contains several YxxI/L motifs reminiscent of LMP2A and a putative TRAF binding site as in LMP1. In latently (persistently) infected BCBL cells the predominant transcript utilizes all eight exons, whereas in phorbol-ester-induced cells, a shorter transcript, lacking exons 4 and 5, is also abundant. We also found evidence for an alternative use of exon 1. Transfection of an epitope-tagged cDNA construct containing all exons indicates that the encoded protein is localized on cell surface and intracellular membranes, and glutathione S-transferase pull-down experiments indicate that its cytoplasmic domain, like that of LMP1, interacts with TRAF1, -2, and -3. Two of 20 KS patients had antibodies to the hydrophilic C-terminal domain, suggesting that the protein is expressed in vivo.

Alternative Splicing↗
PubMed1999

Prevalence of infection with human herpesvirus 8/Kaposi's sarcoma herpesvirus in rural South Africa.

OBJECTIVE: To determine prevalence of infection with human herpesvirus 8 (HHV-8)/Kaposi's sarcoma herpesvirus (KSHV) and to gain some insight into possible transmission dynamics of this novel virus in South Africa. METHODS: Stored, anonymous serum from 50 patients with a sexually transmitted disease (STD), 50 adult medical ward patients (25 male, 25 female), and 36 paediatric ward patients in Hlabisa Hospital, KwaZulu-Natal, was screened by enzyme-linked immunosorbent assay (ELISA) for antibodies to the small capsid-related protein encoded by HHV-8/KSHV orf65. Antibodies to the latency-associated nuclear antigen (LANA) were measured by immunofluorescence, and sera that were reactive in the ELISA but negative by immunofluorescence were re-tested by Western blot against the recombinant orf65 protein to exclude nonspecific reactivity. RESULTS: Overall, 47 patients tested positive (34.6%), 76 tested negative (55.9%) and 13 (9.5%) had indeterminate results. Among those with a definite result, prevalence was similar among males (47.2%) and females (52.8%) and increased in later adulthood (< 18 months 37.5%, 19-120 months 38.5%, 15-34 years 32.1%, 35-69 years 62.8%). Prevalence was highest among medical patients (58.1%); among those with an STD it was 31.1% (P = 0.01), and among children it was 22.8% (P = 0.001). When age-adjusted, prevalence among medical patients (23.7%) was similar to that among patients with an STD. CONCLUSION: Prevalence of HHV-8/KSHV is high in this setting and transmission appears to be occurring in childhood as well as among adults. Larger population-based studies are required to detail the transmission dynamics of HHSV-8/KSHV.

Adult↗
PubMed1998

Seroconversion for human herpesvirus 8 during HIV infection is highly predictive of Kaposi's sarcoma.

BACKGROUND: The finding of antibodies against human herpesvirus 8 (HHV-8) is associated with the occurrence of Kaposi's sarcoma in persons infected with HIV. However, the predictive value of HHV-8 antibodies for Kaposi's sarcoma in HIV infection is unknown. METHODS: The Amsterdam Cohort Studies on HIV infection and AIDS started in 1984 for homosexual men and in 1985 for injecting drug users. Serum samples from 1459 homosexual men and 1167 drug users were tested for antibodies to recombinant HHV-8 lytic-phase capsid (ORF65) antigen and latent-phase nuclear (ORF73) antigen. Individuals were retrospectively identified as HHV-8-positive or HHV-8-negative at enrolment or HHV-8 seroconverter during the study. Kaposi's sarcoma-free survival time was compared between HIV-infected men who were positive for HHV-8 at enrolment and those who later seroconverted for HHV-8. Hazard ratios were estimated for Kaposi's sarcoma, lymphoma, and opportunistic infection according to the HHV-8 serostatus. RESULTS: The incidence of HHV-8 seroconversion among drugs users was 0.7 per 100 person-years based on 31 seroconversions, whereas an incidence of 3.6 was found among homosexual men based on 215 seroconversions. The hazard ratio for Kaposi's sarcoma was 3.15 (95% CI: 1.89-5.25) in HIV-infected individuals if HHV-8 antibodies were present either at enrolment or at HIV seroconversion. In HIV-infected persons who later seroconverted to HHV-8, Kaposi's sarcoma developed more rapidly: hazard ratio of 5.04 (95% CI: 2.94-8.64), an additional risk of 1.60 (95% CI: 1.01-2.53; P = 0.04). Time-dependent adjustment for CD4+ cell count and HIV RNA had no impact on the additional risk, although the CD4+ cell count was an independent risk factor for Kaposi's sarcoma. HHV-8 infection did not increase the risk of AIDS-related lymphoma or opportunistic infections. CONCLUSIONS: The incidence of HHV-8 infection is higher in homosexual men than in drug users. The presence of HHV-8 antibodies in HIV-infected persons increases the risk of Kaposi's sarcoma. Among HIV-infected persons, those who subsequently seroconvert for HHV-8 are at highest risk. These results strongly confirm the causal role of HHV-8 in Kaposi's sarcoma and emphasize the clinical relevance of HHV-8 seroconversion before and after the HIV infection.

Adult↗
PubMed1998

Prevalence and transmission of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents.

We studied the seroprevalence and transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), among 215 Ugandan children, adolescents and young adults. We measured antibodies to a latent nuclear antigen (LANA) and a lytic cycle protein encoded by open reading frame (orf) 65. Infection with KSHV/HHV8 occurred during early childhood and reached adult levels (approx. 50%) before the age of puberty. In children younger than 12 years of age, antibodies to LANA and the orf65 protein were independently associated with hepatitis B infection (p < 0.005). KSHV/HHV8 infection was not associated with antibodies to hepatitis A virus and hepatitis C virus, nor with the quality of the water supply, household size, previous blood transfusions, number of boy/girl friends or marital status. Antibodies to the orf65 protein, but not LANA, were weakly associated with a history of i.v. injections. Our results show that, in contrast to its sexual mode of transmission among homo/bisexual men and sexually transmitted diseases clinic attendees of Northern Europe and the US, transmission of KSHV in Uganda occurs largely before puberty. Among Ugandan children, KSHV transmission follows a horizontal pattern similar to other herpesviruses, in particular the related gamma herpesvirus, Epstein-Barr virus. Transmission of KSHV may be facilitated by living conditions that also promote infection with hepatitis B virus.

Adolescent↗
PubMed1998

The extended packaging sequence of MoMLV contains a constitutive mRNA nuclear export function.

The present report shows that incorporation of defined sequences from the Moloney murine leukaemia virus (MoMLV) into Rex dependent expression vectors based on the human T-cell leukaemia virus (HTLV-1) allows Rex independent gene expression. Deletion mutagenesis of the MoMLV derived sequences allowed this function to be localised to a 312 nt length sequence overlapping the MoMLV gag p15/p12 open reading frame. This 'extended packaging sequence' has been reported to markedly increase the titre of in vitro packaged retroviral vectors. Using fluorescent in situ hybridisation combined with confocal microscopy we show that the 312 nt element can replace Rex mediated nuclear export and expression of transcripts containing HTLV-1 cis acting repressive elements. Our observations are consistent with the extended packaging sequence of MoMLV exerting a constitutive mRNA nuclear export function.

Base Sequence↗