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Biomedical subjects

R A Weiss

Publications and source records attributed to R A Weiss.

At least 127 records · Page 7Linked to original sources

HIV infection and neoplasia.

HIV infection predisposes to several neoplastic conditions, especially non-Hodgkin lymphoma (NHL) and Kaposi's sarcoma (KS), and also intraepithelial cervical neoplasia (CIN) and anal neoplasia (AIN) (but not cervical or anal invasive cancer) and possibly seminoma. For neoplasias associated with oncogenic human viruses (ie, some NHL, CIN, AIN, and probably KS) the role of HIV is most probably linked to its immunosuppressive effect and interference with immune-mediated tumour surveillance. HIV-1, through its regulatory protein tat, might also have a direct promoting effect on KS lesions but it is not essential for their development. The increased frequency of Burkitt's lymphoma and Epstein-Barr-virus-negative large-cell lymphoma in AIDS patients, but not in immunosuppressed transplant patients, and the increased rate of testicular tumours in HIV-infected individuals remain unexplained and may indicate either a direct role for HIV or other cofactors.

Acquired Immunodeficiency Syndrome↗

Endogenous D-type (HERV-K) related sequences are packaged into retroviral particles in the placenta and possess open reading frames for reverse transcriptase.

All primates studied to date produce retroviral-like particles in their placentae. We have purified these particles from two primate species, one Old World (human) and one New World (marmoset), and have identified the retroviral sequences which are packaged into these particles. Three families of sequences have been detected in these particles in human, all of which have the highest homology to B- and D-type retroviruses and to the human endogenous retrovirus HERV-K10. Previous studies have reported that the New World monkeys do not possess sequences with homology to HERV-K10. We have identified a new family of low-copy-number sequences which are present in New World monkeys and which possess 70% homology to the HERV-K family. Particles from both species possess reverse transcriptase activity and we have found that some of these retroviral particles package sequences which encode long open reading frames in pol, as revealed by expression cloning in Escherichia coli. These open reading frames could encode the reverse transcriptase enzyme activity found in the particles.

Animals↗

Hot fusion of HIV.

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CD4 Antigens↗

Comparison of efficiency of infection of human gene therapy target cells via four different retroviral receptors.

The relative efficiency of transduction of gene therapy target cells was measured for retroviruses bearing the envelopes of amphotropic murine leukemia virus (MLV-A), xenotropic murine leukemia virus (MLV-X), gibbon ape leukemia virus (GALV), feline leukemia virus subgroup B (FeLV-B), and the feline endogenous virus RD114. These viruses use various cell-surface receptors. Activated peripheral blood lymphocytes (PBL) and primary melanoma cultures were infected relatively poorly by MLV-X pseudotypes. RD114 pseudotypes infected PBL relatively well, whereas bone marrow progenitor cells were efficiently infected by all viruses. Helper-free virus bearing the envelopes of MLV-A, RD114, or GALV was similarly tested. All infected melanoma or bone marrow progenitor cells efficiently, whereas MLV-A was relatively inefficient for infection of PBL. The general utility of RD114 pseudotyped virus for gene delivery coupled with its resistance to inactivation by human serum makes this envelope the most suitable choice for in vivo gene therapy.

Base Sequence↗

Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa. Uganda Kaposi's Sarcoma Study Group.

BACKGROUND: Endemic Kaposi's sarcoma (KS) is a clinically and epidemiologically distinct human immunodeficiency virus negative form of KS occurring in Africa. Kaposi's sarcoma is now the most frequently reported cancer in some areas of Africa. OBJECTIVE: To determine if a KS-associated herpesvirus (KSHV) is present in both endemic HIV-seronegative and HIV-seropositive KS lesions from African patients. METHODS: Paraffin-embedded tissue specimens from Ugandan patients with KS and non-KS tumor control patients attending a university-based oncology clinic were examined in a blinded case-control study. Tissue DNA specimens were examined for detectable KSHV genome by nested polymerase chain reaction performed at two independent laboratories. RESULTS: We identified KSHV in 17 (85%) of 20 KS tissue specimens from HIV-seronegative patients and 22 (92%) of 24 KS tissue specimens from HIV-infected persons. Kaposi's sarcoma lesions from four HIV-infected persons and four HIV-seronegative persons were positive for KSHV. Unlike previous studies in North America and Europe, three (14%) of 22 non-KS cancer control patients' tissue specimens were also positive for KSHV that resulted in an overall odds ratio of 49.2 (95% confidence interval, 9.1 to 335) for detecting KSHV in KS lesions from patients in Uganda. CONCLUSION: As in North America and Europe, KSHV infection is strongly associated with both HIV-seropositive and HIV-seronegative KS in Africa. However, it is likely that infection with this virus is more highly prevalent in Uganda.

Case-Control Studies↗

Sensitization of cells and retroviruses to human serum by (alpha 1-3) galactosyltransferase.

Mammalian C-type retroviruses are inactivated by human serum, following triggering of the classical complement cascade. This may have inhibited transmission to humans of C-type oncoviruses from other mammals. Indeed, the retroviruses human immunodeficiency virus and human T-cell leukaemia virus are resistant to human complement. Antibody-independent activation of human C1q, the first component of the classical pathway, by retroviral envelope proteins has been described. However, retroviruses produced from human cells are resistant to inactivation by human complement and human serum is known to contain antibodies directed against carbohydrates on retroviral envelopes. Gal(alpha 1-3)Gal terminal carbohydrates are expressed by most mammals but are absent in humans, which lack a functional (alpha 1-3)galactosyltransferase gene. Here, we demonstrate that anti-Gal(alpha 1-3)Gal antibodies in human serum inactivate retroviruses produced from animal cells. Expression of porcine (alpha 1-3)galactosyltransferase in human cells renders the cells and the retroviruses they produce sensitive to human serum.

3T3 Cells↗

Retrovirus classification and cell interactions.

Retroviruses cause a variety of diseases such as cancer, AIDS, autoimmunity and diseases of central nervous system, bone and joints. Some retroviruses are apparently harmless and some retroviral genomes are even inherited as host mendelian traits. Whereas oncoviruses generally have a low virus load, so that antiviral therapy would not greatly affect disease progression, lentiviruses like HIV have high load and turnover. The cell interactions of retroviruses largely determine their pathogenesis. Finally, retroviruses are being exploited therapeutically as vectors for gene therapy.

Animals↗

Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry.

A panel of primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates that infected several CD4+ T-cell lines, including MT-2 and C8166, were tested for infection of blood-derived macrophages. Infectivity titers for C8166 cells and macrophages demonstrated that primary SI strains infected macrophages much more efficiently than T-cell line-adapted HIV-1 strains such as LAI and RF. These primary SI strains were therefore dual-tropic. Nine biological clones of two SI strains, prepared by limiting dilution, had macrophage/C8166 infectivity ratios similar to those of their parental viruses, indicating that the dual-tropic phenotype was not due to a mixture of non-SI/macrophage-tropic and SI/T-cell tropic viruses. We tested whether the primary SI strains used either Lestr (fusin) or CCR5 as coreceptors. Infection of cat CCC/CD4 cells transiently expressing Lestr supported infection by T-cell line-adapted strains including LAI, whereas CCC/CD4 cells expressing CCR5 were sensitive to primary non-SI strains as well as to the molecularly cloned strains SF-162 and JR-CSF. Several primary SI strains, as well as the molecularly cloned dual-tropic viruses 89.6 and GUN-1, infected both Lestr+ and CCR5+ CCC/CD4 cells. Thus, these viruses can choose between Lestr and CCR5 for entry into cells. Interestingly, some dual-tropic primary SI strains that infected Lestr+ cells failed to infect CCR5+ cells, suggesting that these viruses may use an alternative coreceptor for infection of macrophages. Alternatively, CCR5 may be processed or presented differently on cat cells so that entry of some primary SI strains but not others is affected.

CD4-Positive T-Lymphocytes↗

Human endogenous retrovirus expression and reverse transcriptase activity in the T47D mammary carcinoma cell line.

We have examined the human mammary tumor cell line T47D and have found that these cells produce virus-like particles which band at the typical density for retroviral particles on a sucrose gradient, possess reverse transcriptase activity, and package HERV-K10-like sequences. Using this information and a bacterial expression system to identify long open reading frames, we have identified individual clones which have full-length open reading frames for reverse transcriptase and RNase H and which could encode the reverse transcriptase activity detected in these cells.

Base Sequence↗

Magnetic resonance imaging findings in a case of advanced Coats' disease.

Coats' disease is an idiopathic, primary vascular anomaly of the retina often presenting with retinal detachment. In this report, the unusual radiologic findings of a 17-month-old patient with advanced Coats' disease are discussed. Computed tomography (CT) showed diffuse increased density of the right eye. Magnetic resonance imaging (MRI) demonstrated moderately hyperintense signal intensity on T1-weighted images, mildly hypointense signal intensity on T2-weighted images, and linear enhancement of the leaves of the detached retina with intense enhancement in the retinal periphery following gadolinium-diethylenetriamine penta-acetic acid (DTPA) contrast administration. The hypointense T2-weighted images and the linear enhancement of the detached retina have not been reported previously in cases of Coats' disease. These observations correlated with the histopathologic features, which showed a totally detached retina containing large telangiectatic vesses and a supretinal space occupied by eoinophilic proteinaceous exudates containing abundant cholesterol crystals. It appears that the MRI characteristics observed in Coats' disease may vary depending on the nature of the subretinal exudate and the severity of the disease.

Eye Enucleation↗