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T F Schulz

Publications and source records attributed to T F Schulz.

At least 55 records · Page 3Linked to original sources
PubMed1998

Risk factors for Kaposi's-sarcoma-associated herpesvirus (KSHV/HHV-8) seropositivity in a cohort of homosexual men, 1981-1996.

A newly identified herpesvirus has been associated with Kaposi's sarcoma. We determined risk factors for Kaposi's-sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) seropositivity and incidence of infection over time in a cohort of Danish homosexual men followed from 1981 to 1996. Antibodies to a latent nuclear (LANA) and a structural (orf65) antigen of KSHV/HHV-8 were measured by immunofluorescence and ELISA/WB respectively. Through linkage with the national AIDS registry, all cohort members diagnosed with AIDS as of September 1996 were identified and their hospital records were scrutinized to record all diagnoses of KS. Overall, 21.1% (52/246) of the men were KSHV/HHV-8-seropositive in 1981. Among the initially seronegative, the rate of KSHV/HHV-8 seroconversion was highest between 1981 and 1982 and declined steadily thereafter. In a multivariate analysis of the status at enrollment in 1981, KSHV/HHV-8 seropositivity was not associated with age but was independently associated both with number of receptive anal intercourses (OR = 2.83; p = 0.03) and with sex with US men (OR = 2.27; p < 0.05). In a multivariate analysis of follow-up data, risk of KSHV/HHV-8 seroconversion was independently associated with having visited homosexual communities in the United States, and current HIV-positive status. More than 5 years' homosexual experience was associated with an insignificantly increased risk (RR = 2.68). KS occurred only in HIV-positive men who were KSHV/HHV-8-positive at or prior to their KS diagnosis. In conclusion, KSHV/HHV-8 appears to be sexually transmitted, probably by receptive anal intercourse, and may have been introduced to Danish homosexual men via sex with US men. The epidemic of KSHV/HHV-8 is now declining. These findings are concordant with the view that KSHV/HHV-8 may have been actively spread simultaneously with and by the same activities that lead to the spread of HIV.

Adolescent↗
PubMed1998

HTLV-I associated primary CNS T-cell lymphoma.

Primary T-cell lymphoma of the central nervous system (CNS) is an extremely rare tumour. The Human T-cell lymphoma virus type 1 associated Adult T-cell lymphoma/leukaemia (ATLL) often involves the CNS during its course but disease limited to the CNS is exceptional. Using clinicopathological and molecular biological information we describe a case of primary CNS ATLL with infiltration of the brainstem associated with an atypical Herpes simplex encephalitis the distribution of which corresponded to that of the tumour. CNS involvement in ATLL is discussed.

Adult↗
PubMed1998

Nucleocytoplasmic transport of HTLV-1 RNA is regulated by two independent LTR encoded nuclear retention elements.

Appropriate expression of HTLV-1 genes requires transcriptional transactivation by Tax and post-transcriptional regulation by Rex, both mediated by LTR encoded RNA sequences. Using a combination of deletion mutagenesis, Rex-reporter CAT assays, fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy it was established that in the absence of Rex, CAT mRNAs harboring HTLV-1 LTR sequences were unable to leave the nucleus. Deletion of the known U5 encoded cis-acting repressing sequence (CRS) led to a partial release of nuclear retention. A novel regulatory element overlapping the 3' Rex responsive element (RxRE) region was shown to prevent export and expression of these transcripts. Deletion of both the 5' LTR encoded CRS and 3' LTR encoded downstream repressive sequence (3' CRS) led to constitutive mRNA nuclear export and gene expression, independently of Rex. The locations of the two regulatory elements indicate that while the 5' CRS selectively acts to hinder export of unspliced transcripts, the 3' CRS has the capacity to induce nuclear retention of all HTLV-1 transcripts, and therefore could potentially contribute to viral latency in infected cells.

Animals↗
PubMed1998

Interassay correlation of human herpesvirus 8 serologic tests. HHV-8 Interlaboratory Collaborative Group.

To standardize human herpesvirus 8 (HHV-8) antibody assays for application to asymptomatic infection, a blinded comparison was done of seven immunofluorescence assays and ELISAs. Five experienced laboratories tested a serum panel from 143 subjects in 4 diagnostic groups. Except for a minor capsid protein ELISA, the other six tests detected HHV-8 antibodies most frequently in classic (80%-100%) and AIDS-related (67%-91%) Kaposi's sarcoma, followed by human immunodeficiency virus-seropositive patients (27%-60%), and least frequently in healthy blood donors (0-29%). However, these six assays frequently disagreed on individual sera, particularly for blood donor samples. Current HHV-8 antibody tests have uncertain accuracy in asymptomatic HHV-8 infection and may require correlation with viral protein or nucleic acid detection. Antibody assays are useful for epidemiologic investigations, but the absolute prevalence of HHV-8 infection in the United States cannot yet be determined.

AIDS-Related Opportunistic Infections↗
PubMed1998

Kaposi sarcoma-associated herpesvirus/human herpesvirus 8, cytokines, growth factors and HIV in pathogenesis of Kaposi's sarcoma.

Epidemiological studies have strengthened the case for Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 being the long-sought Kaposi sarcoma agent, but have also pointed to a role for other co-factors. Like other tumour viruses, Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 establishes a latent (persistent) infection in Kaposi sarcoma-spindle (tumorous) cells, but can also undergo lytic replication in these and other cell types. Several latent and lytic viral genes may play a role in the pathogenesis of Kaposi's sarcoma. Although Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 contains at least two genes with transforming properties, it has not yet been shown to be oncogenic in animals. This, and other studies on inflammatory/angiogenic cellular and viral cytokines as well as HIV-Tat, emphasizes the multifactorial complexity of the pathogenesis of Kaposi's sarcoma.

Journal Article↗
PubMed1997

The human T-cell lymphotropic viruses types I/II are not involved in T prolymphocytic leukemia and large granular lymphocytic leukemia.

The possible involvement of the human T lymphotropic viruses type I and II (HTLV-I and -II) in lymphoproliferative disorders of mature T cells other than adult T cell leukemia/lymphoma (ATLL) has been controversial. Most studies have focused primarily on the cutaneous T cell lymphomas. However, skin involvement is a frequent feature of T prolymphocytic leukemia (T-PLL) and antibodies against HTLV-I and -II have been reported in individuals with large granular lymphocytic (LGL) leukemia. We examined 36 patients with T-PLL and 28 with LGL leukemia for evidence of HTLV-I and -II. Polymerase chain reaction (PCR) was performed on DNA from fresh peripheral blood mononuclear cells (PBMCs) and PBMCs after short-term culture (STC) using primers against all parts of the HTLV-I genome (LTR, gag, env, pol, tax/rex) and against HTLV-II pol and gag. Reverse transcriptase (RT) activity was measured on supernatants from STCs using a sensitive PCR-based technique. No HTLV-I or -II sequences were found by PCR nor RT activity detected in the 64 cases. Our findings do not provide evidence of HTLV-I or -II infection in T-PLL and LGL leukemia patients from an HTLV-I nonendemic area. Previous positive reports on these disorders may represent technical artefacts, detection of endogenous HTLV-like sequences or reflect patients from endemic areas and a variable etiology of T cell diseases.

Human T-lymphotropic virus 1↗
PubMed1997

Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection: an international study.

Association between mycosis fungoides (MF), its leukaemic variant Sezary syndrome (SS) and the human T-cell lymphotropic virus type-I (HTLV-I) has been controversial, with the reported incidence of infection varying between 0% and nearly 100%. We studied 127 patients (85 MF, 28 SS, five Sezary cell leukaemia, four lymphomatoid papulosis, and five unspecified cutaneous T-cell lymphomas (CTCL)) originating from Europe (France, Spain, U.K., Portugal) or from U.S.A. (California) for the presence of HTLV-I infection markers. HTLV-I and -II serology were performed on 78 patients using standard immunological methods. Reverse transcriptase (RT) assay was also performed in 26 cases using an RT-PCR-based method of high sensitivity. Molecular analyses were performed on 215 DNA samples (121 from fresh PBMCs, 26 from PBMCs after short-term culture and 68 from skin lesions) by PCR amplification using HTLV-I and -II gag, pol, env, pX and LTR specific primers. Immunological tests were negative except for two sera which were indeterminate. PCR with all HTLV-I and -II primer pairs showed negative results in all 215 samples investigated. No RT activity was detected in short-term PBMC cultures of any of the 26 cases studied. The results of this large study from five different countries clearly indicate that MF and SS are not associated with HTLV-I infection.

Blotting, Western↗
PubMed1997

Human herpesvirus 8 infection occurs following adolescence in the United States.

Most recent evidence suggests that human herpesvirus 8 (HHV-8) infection is restricted to persons with Kaposi's sarcoma (KS) or to persons who may subsequently develop KS. To accurately determine the prevalence of infection in the United States, children and adults with AIDS were examined for evidence of HHV-8 infection to see whether HHV-8 (like other herpesviruses) would be readily detected in immunosuppressed persons. By use of nested polymerase chain reaction, DNA specific for HHV-8, Epstein-Barr virus, and cytomegalovirus was detected in blood leukocytes from 0, 26 (51%), and 9 (18%), respectively, of 51 children. Similarly, HHV-8-specific antibodies were not detected in analyses of sera from the children. By contrast, HHV-8 DNA was detected in 9 (27%) of 33 adult AIDS patients without KS. These findings suggest that the pattern of transmission of HHV-8 in the United States differs from that of other herpesviruses in that primary infection occurs predominantly in adults.

AIDS-Related Opportunistic Infections↗
PubMed1997

Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but not healthy semen donors.

OBJECTIVE: To ascertain the prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus (HHV) type 8, and cytomegalovirus (CMV) DNA in semen was investigated. METHODS: Amplification by nested polymerase chain reaction was used to detect viral DNA sequences in samples from 24 HIV-infected gay men, 15 of them with Kaposi's sarcoma (KS), and 115 healthy donors. RESULTS: Six of the 24 HIV-infected patients had detectable HHV-8 DNA in their semen: three of the 15 patients with KS and three of the nine patients without KS. CMV DNA was detected in 20 semen samples from HIV-infected patients. None of the semen samples from healthy donors had detectable HHV-8 DNA and rates of CMV DNA detection were low (3%). CONCLUSIONS: The study demonstrates the presence of HHV-8 in semen from HIV-infected individuals with, or at risk, of developing KS and the potential for sexual transmission of the virus. We found no evidence of HHV-8 in the semen of HIV-uninfected donors.

Cytomegalovirus↗
PubMed1997

The CD4-independent tropism of human immunodeficiency virus type 2 involves several regions of the envelope protein and correlates with a reduced activation threshold for envelope-mediated fusion.

Several human immunodeficiency virus type 2 (HIV-2) strains have been shown to infect some CD4-negative cell lines (P. R. Clapham, A. McKnight, and R. A. Weiss, J. Virol. 66:3531-3537, 1992). Using molecular clones of HIV-2 with a CD4-independent tropism, we have identified critical amino acid residues in the envelope protein which are required for CD4-independent infection. Mutations located immediately upstream of a proposed coiled coil domain in the transmembrane protein (A526T or I528M) and flanking the base of the V4 loop (L378F and K403R) are crucial for the CD4-independent phenotype. Of several mutations conferring a positive charge in V1, V2, and V3, only the change in V3 (Q310K) helped to enhance the CD4-independent phenotype but could not mediate it on its own. These mutations reduce the amount of soluble CD4 required to trigger CD4-independent cell-cell fusion, suggesting that they lower the activation threshold for the fusion process. After binding to cell surface-anchored CD4, a CD4-independent recombinant envelope protein showed an increased binding of anti-envelope protein antibodies, suggesting either an enhanced binding to cell surfaces or more extensive conformational changes in CD4-independent compared to CD4-dependent envelope proteins. The reduced activation threshold of CD4-independent envelope proteins may thus enable them to utilize a membrane molecule for entry which is not as efficient as CD4 in triggering the conformational changes required for the membrane fusion process. CD4-independent HIV-2 variants may be conceptually similar to influenza virus variants capable of fusing at a higher than normal pH (R. S. Daniels, J. C. Downie, J. A. Hay, M. Knossow, J. J. Skehel, M. L. Wang, and D. C. Wiley, Cell 40:431-439, 1985).

CD4 Antigens↗
PubMed1997

Biological characterization of human immunodeficiency virus type 1 clones derived from different organs of an AIDS patient by long-range PCR.

In order to characterize the biological properties of human immunodeficiency virus type 1 (HIV-1) variants from different tissues (peripheral blood mononuclear cells [PBMC], lymph node, spleen, brain, and lung) of one patient, we have chosen long-range PCR to amplify virtually full-length HIV proviruses and to construct replication-competent viruses by adding a patient-specific 5' long terminal repeat. To avoid selection during propagation in CD4+ target cells, we transfected 293 cells and used the supernatants from these cells as challenge viruses for tropism studies after titration on human PBMC. Despite differences in the V3 loop of the major variants found in brain and lung compared to lymphoid tissues all recombinant HIV clones obtained showed identical cell tropism and replicative kinetics. After infection of human PBMC these viruses replicated with similar kinetics, with a slow/low-titer, non-syncytium-inducing phenotype. In contrast to the prediction of macrophage tropism, drawn from the V3 loop sequence, none of these viruses infected monocyte-derived macrophages. The challenge of blood dendritic cells by these recombinant viruses in the presence of tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and interleukin-4 resulted in a productive infection only after adding stimulated CD4+ T lymphocytes. Therefore, the biological properties of the HIV-1 variants derived from nonlymphoid tissue of this patient did not differ from those of HIV-1 variants from lymphoid tissue with respect to tropism for primary cells such as PBMC, macrophages, and blood dendritic cells.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The 222- to 234-kilodalton latent nuclear protein (LNA) of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) is encoded by orf73 and is a component of the latency-associated nuclear antigen.

Kaposi's sarcoma (KS)-associated herpesvirus or human herpesvirus 8 (KSHV/HHV8) is the likely cause of KS and primary effusion lymphomas or body cavity-based lymphomas (BCBLs). A latency-associated nuclear immunofluorescence antigen (LANA) (D. H. Kedes, E. Operskalski, M. Busch, R. Kohn, J. Flood, and D. Ganem, Nat. Med. 2:918-924, 1996; S. J. Gao, L. Kingsley, M. Li, W. Zheng, C. Parravicini, J. Ziegler, R. Newton, C. R. Rinaldo, A. Saah, J. Phair, R. Detels, Y. Chang, and P. S. Moore, Nat. Med. 2:925-928, 1996) and a 222- to 234-kDa nuclear protein (LNA) (S. J. Gao, L. Kingsley, D. R. Hoover, T. J. Spira, C. R. Rinaldo, A. Saah, J. Phair, R. Detels, P. Parry, Y. Chang, and P. S. Moore, N. Engl. J. Med. 335:233-241, 1996) have previously been described in BCBL cell lines by immunofluorescence and Western blotting techniques, respectively. To identify the viral gene(s) encoding this antigen(s) we screened a cDNA library from HBL-6 cells, a B-cell lymphoma cell line persistently infected with KSHV/HHV8, with KS patient sera. One set of positive clones contained the 3' end of orf73, as well as the complete orf72 and orfK13, and another set contained the 5' end of orf73. Comparison of cDNA sequences with the KSHV/HHV8 genomic sequence revealed a splice event, occurring upstream of orf73. Immunoaffinity purified antibodies to a recombinant carboxy-terminal fragment of the orf73-encoded protein showed the characteristic speckled nuclear immunofluorescence pattern of LANA and reacted with the 222- to 234-kDa LNA on Western blots. Expression of full-length orf73 in bacteria and COS7 cells reproduced the LNA banding pattern. Immunohistochemistry on cases of nodular KS revealed that orf73/LNA is expressed in the nucleus of KS spindle cells. These findings demonstrate that orf73 encodes the 222- to 234-kDa LNA, is a component of LANA, and is expressed in KS tumor cells.

Animals↗