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Biomedical subjects

M D Daniel

Publications and source records attributed to M D Daniel.

At least 55 records · Page 3Linked to original sources
PubMed1989

Genetic diversity of simian immunodeficiency virus.

We have demonstrated that the genetic diversity of simian immunodeficiency virus from African green monkeys (SIVagm) is much greater than that observed previously for individual HIV-1, HIV-2, or SIVmac isolates. Extensive genetic variation among SIVagm isolates and the high prevalence of green monkey infection without disease suggest that the virus has been in the green monkey population for a long time. We have also demonstrated that SIV from a sooty mangabey monkey (isolate SMM-7) is closer to SIVmac and HIV-2 than to HIV-1 and SIVagm. The extensive genetic diversity of SIVagm and the relatedness of SIVsmm to HIV-2 warrant continued examination of SIVagm and SIVsmm isolates from dispersed geographic regions. SIV strains much more closely related to HIV-1, HIV-2, or SIVmac may be found which would be reasonable candidates for recent cross-species transmission.

Animals↗
PubMed1989

Use of infectious molecular clones of simian immunodeficiency virus for pathogenesis studies.

Three infectious molecular clones of SIVmac and one of HIV-2 exhibit remarkable variation in their biological properties despite similarities in genome organization and sequence relatedness. Cloned viruses differed in their ability to grow in various cultured cells, in their ability to infect macaques, and in the location of the env stop codon. Sequences from the 3' end predict that at least three of the four clones do not have an intact, functional nef gene. All four cloned viruses yield infectious virus in HUT-78 and all four cloned viruses are cytopathic.

Animals↗
PubMed1988

Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys.

The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme-linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero-positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease.

Animals↗
PubMed1988

Comparison of simian immunodeficiency virus isolates.

Information on the extent of genetic variability among non-human primate lentiviruses related to human immunodeficiency virus (HIV) is sorely lacking. Here we describe the isolation of two molecular clones from the simian immunodeficiency virus (SIV) and their use to derive restriction endonuclease maps of five SIV isolates from rhesus macaques and one from a cynomolgus macaque. Although similar, all six viral isolates are readily distinguishable; the single isolate from a cynomolgus macaque is the most different. The restriction endonuclease map of one macaque isolate (SIVMAC-251) is identical to that published by others for STLV-IIIAGM of African green monkeys and for HTLV-IV of humans. Nucleotide sequences from the envelope region of cloned SIVMAC-251 have more than 99% identify to previously published sequences for STLV-IIIAGM (refs 2, 4) and HTLV-IV (ref. 4). These results and other observations provide strong evidence that isolates previously referred to as STLV-IIIAGM and HTLV-IV by others are not authentic, but were derived from cell cultures infected with SIVMAC-251.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Simian immunodeficiency virus-induced meningoencephalitis: natural history and retrospective study.

Simian immunodeficiency virus (SIV) is a lentivirus with morphological and antigenic similarities to human immunodeficiency virus, the causative agent of acquired immunodeficiency syndrome (AIDS) of humans. Macaque monkeys infected with SIV show profound immunological impairment, clinically characterized by multiple opportunistic infections and neoplasms. Retrospective examination of autopsy tissue from 27 SIV-infected animals demonstrated that approximately 60% of the experimentally inoculated animals had a meningoencephalitis characterized by perivascular infiltrates of macrophages and multinucleate giant cells in the white and gray matter and leptomeninges. Ultrastructurally, these macrophages contained typical lentiviral particles within membrane-bound intracytoplasmic vacuoles. Other findings in the central nervous system included discrete randomly located neuroglial nodules, endothelial hypertrophy, and leptomeningeal thickening. The results indicate tha the meningoencephalitis induced by SIV in monkeys is similar to the lesions of the central nervous system in patients with AIDS and that SIV infection in the macaque is a useful animal model to study the pathogenesis of human immunodeficiency virus--related subacute encephalitis or AIDS encephalopathy.

Animals↗
PubMed1988

Simian immunodeficiency virus from African green monkeys.

Simian immunodeficiency virus (SIV) was isolated from the total peripheral blood mononuclear cell population and the monocyte-macrophage adherent cell population of three seropositive green monkeys originating from Kenya. SIV from these African green monkeys (SIVagm) was isolated and continuously produced with the MOLT-4 clone 8 (M4C18) cell line but not with a variety of other cells including HUT-78, H9, CEM, MT-4, U937, and uncloned MOLT-4 cells. Once isolated, these SIVagm isolates were found to replicate efficiently in M4C18, SupT1, MT-4, U937, and Jurkat-T cells but much less efficiently if at all in HUT-78, H9, CEM, and MOLT-4 cells. The range of CD4+ cells fully permissive for replication of these SIVagm isolates thus differs markedly from that of previous SIV isolates from macaques (SIVmac). These SIVagm isolates had a morphogenesis and morphology like that of human immunodeficiency virus (HIV) and other SIV isolates. Antigens of SIVagm and SIVmac cross-reacted by comparative enzyme-linked immunosorbent assay only with reduced efficiency, and optimal results were obtained when homologous antibody and antigen were used. Western blotting (immunoblotting) of purified preparations of SIVagm isolate 385 (SIVagm385) revealed major viral proteins of 120, 27, and 16 kilodaltons (kDa). The presumed major core protein of 27 kDa cross-reacted antigenically with the corresponding proteins of SIVmac (28 kDa) and HIV-1 (24 kDa) by Western blotting. Hirt supernatant replicative-intermediate DNA prepared from cells freshly infected with SIVagm hybridized to SIVmac and HIV-2 DNA probes. Detection of cross-hybridizing DNA sequences, however, required very low stringency, and the restriction endonuclease fragmentation patterns of SIVagm were not similar to those of SIVmac and HIV-2. The nucleotide sequence of a portion of the pol gene of SIVagm385 revealed amino acid identities of 65% with SIVmac142, 64% with HIV-2ROD, and 56% with HIV-1BRU; SIVagm385 is thus related to but distinct from previously described primate lentiviruses SIVmac, HIV-1, and HIV-2. Precise information on the genetic makeup of these and other SIV isolates will possibly lead to better understanding of the history and evolution of these viruses and may provide insight into the origin of viruses that cause acquired immunodeficiency syndrome in humans.

Animals↗
PubMed1988

Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac.

Infection of macaque monkeys with simian immunodeficiency virus (SIV) is probably the best animal model currently available for studying acquired immunodeficiency syndrome. In this report, we describe three infectious molecular clones of SIVmac and one of human immunodeficiency virus type 2 (HIV-2) and their use in the study of cell and species specificity, animal infection, and the relationship of gene sequence to function. Replication of the cloned viruses in different cell lines varied dramatically. Some human CD4+ cell lines (HUT 78 and MT-4) supported the replication of SIVmac and HIV-2, while others (CEM and Jurkat-T) supported the replication of HIV-2 but not SIVmac. Growth of cloned virus in macaque lymphocytes in vitro was predictive of macaque infection in vivo. Macaque lymphocytes supported the replication of SIVmac239 and SIVmac251 but not SIVmac142 or HIV-2ROD. Using virus recovery and antibody response as criteria for infection, macaques that received cloned SIVmac251 and SIVmac239 became infected, while macaques receiving cloned SIVmac142 and HIV-2ROD did not become infected. Nucleotide sequences from the envelope region of all four cloned viruses demonstrated that there is considerable flexibility in the location of the translational termination (stop) signal. These infectious molecular clones will be very useful for future studies directed at the molecular basis for persistence, pathogenicity, tropism, and cell and species specificity.

Amino Acid Sequence↗
PubMed1987

Long-term persistent infection of macaque monkeys with the simian immunodeficiency virus.

Juvenile rhesus macaques 6 to 18 months of age were experimentally infected by intravenous inoculation with the simian immunodeficiency virus (SIV), the T cell-tropic retrovirus of monkeys related to the human acquired immunodeficiency syndrome (AIDS) virus HIV. The SIV used for inoculation was grown either in normal human peripheral blood lymphocytes in the presence of interleukin 2 or in the human tumour cell line HUT-78. Eight of the macaques died 129 to 352 days post-inoculation with a variety of clinical and pathological findings paralleling those of AIDS in humans. However eight other animals became persistently infected for prolonged periods; these eight macaques remained alive at 537 and 820 days post-inoculation despite persistent lymphadenopathy and our continued ability to isolate SIV. The ability of these monkeys to survive infection correlated directly with the strength of their antibody response to SIV. Infection was also established in macaques using approximately 100 tissue culture infectious doses of HUT-78-grown SIV. There was no correlation between the dose of virus inoculum and either the strength of the antibody response or clinical outcome. These results demonstrate that SIV infection of macaques can be used not only to study acute AIDS but also to mimic the long-term persistent infection seen in carriers of HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunophenotypic characterization of the cutaneous exanthem of SIV-infected rhesus monkeys. Apposition of degenerative Langerhans cells and cytotoxic lymphocytes during the development of acquired immunodeficiency syndrome.

A T-cell tropic retrovirus, simian immunodeficiency virus (SIV), has recently been isolated from immunodeficient rhesus monkeys. This virus has remarkable similarities to human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome. Subsequent studies of simian infection with SIV have shown it to be a relevant animal model for studying the pathogenesis of AIDS in man. In both HIV-infected humans and SIV-infected monkeys, a cutaneous maculopapular eruption has been described. To date, the pathogenesis and possible relationship of these exanthema to the evolution of systemic immunosuppression have remained obscure. In this study, the mononuclear cell infiltrates that characterize skin rashes of SIV-infected rhesus monkeys were found to be composed predominantly of cells with phenotypic characteristics of cytotoxic/suppressor (T8+) lymphocytes and natural killer cells. Many of these cells expressed membrane-bound interleukin-2 receptor molecules. Double labeling and immunoelectron microscopy revealed these cells in direct contact with degenerative Langerhans cells within the epidermis and dermis. These observations suggest that the cutaneous rash associated with SIV infection may be the consequence of target cell injury of Langerhans cells by effector cells with cytotoxic potential.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV).

A T-cell tropic lentivirus of macaques the simian immunodeficiency virus (SIV), has morphologic, growth, and antigenic properties that indicate that it is related to the human immunodeficiency virus (HIV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Six juvenile macaques developed persistent lymphadenopathy (greater than 3 months in duration) after inoculation with SIV. The histologic appearance of the lymph nodes was characterized by marked follicular hyperplasia with abundant proliferative B cells infiltrating into the paracortex. The number of T8-positive lymphocytes equaled or exceeded the number of T4-positive lymphocytes in the paracortex. These findings, in association with immunologic abnormalities and a previously observed fatal immunodeficiency syndrome in SIV-infected macaques, provide further evidence of the importance of SIV-induced disease in macaques as a model for the study of AIDS.

AIDS-Related Complex↗
PubMed1987

Simian models for AIDS.

The macaque immunodeficiency syndrome has many parallels to AIDS in humans. Affected monkeys develop profound, prolonged T lymphocyte dysfunction and die of lymphomas or opportunistic infections. We recently isolated a virus that we call SIV from four sick macaque monkeys. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of human AIDS. The pathogenicity of this newly isolated virus was tested in macaque monkeys. Five of six died between 127 and 352 days following inoculation. The animals developed a wasting syndrome and died with adenovirus pancreatitis and/or pneumonia and primary retroviral encephalitis. Immunological abnormalities in these animals included a decrease in circulating T4+ lymphocytes and depressed peripheral blood lymphocyte proliferative response to pokeweed mitogen. The SIV monkey model holds great promise for testing antiviral agents and for the development of vaccines against AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Lymphoproliferative syndrome in an immunodeficient rhesus monkey naturally infected with an HTLV-III-like virus (STLV-III).

A rhesus monkey with a naturally acquired STLV-III infection developed immunosuppression and a lymphoproliferative syndrome characterized by progressive lymphadenopathy and widespread visceral mononuclear cell infiltration. On microscopic examination, diffuse sheets of plasmacytoid lymphoblasts obliterated the sinuses and follicles of the nodes, replaced normal cellular elements of the spleen, bone marrow, and thymus, and infiltrated the lung, liver, kidney, salivary gland, pancreas, thyroid, stomach, and tongue. Immunohistologic studies indicated that the predominant cell in these infiltrates was a B lymphocyte, of oligo- or polyclonal origin. Similar but less extreme lymphoproliferative abnormalities were seen at necropsy in a substantial number of other animals with naturally occurring macaque immunodeficiency syndrome. The present case represents the first prospectively studied monkey with a naturally acquired simian T lymphotropic virus type III infection and illustrates an important manifestation of disease associated with such an infection.

Acquired Immunodeficiency Syndrome↗
PubMed1986

[Prognosis of hemolytic uremic syndrome in children. Importance of extrarenal involvement].

The prognosis of hemolytic uremic syndrome was studied in 37 children hospitalized between January 1980 and January 1985. 75% of affected children were less than 3 years of age. Twenty-two (60%) presented with anuria or oliguria (mean duration of anuria: 10.7 days). In this last group, severe extrarenal manifestations occurred: 12 cases of neurological involvement (6 involving hypervolemia), gastrointestinal involvement in 5 cases, including a case of ileal necrosis; pancreatic involvement in another. Three children died during the first month of the disease (overall death-rate: 8%). Thirty-two children were followed with a mean 24 months follow-up (6 months to 60 months). Six (19%) presented with sequellae, of which 3 were severe: one severe arterial hypertension and two with chronic renal failure of which one terminal with severe neurologic sequellae. The existence of extrarenal manifestations implies a poor prognosis. Among the 22 children with anuria or oliguria, 8 had no extra-renal manifestations. All of these recovered. Three of 11 children with one extrarenal manifestation had an unfavorable outcome. The course was unfavorable in the 3 cases with multiple extrarenal involvement.

Anuria↗
PubMed1985

Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III.

The T-cell tropic retrovirus of macaque monkeys STLV-III has morphologic, growth, and antigenic properties indicating that it is related to HTLV-III/LAV, the etiologic agent of the acquired immune deficiency syndrome (AIDS) in humans. Four of six rhesus monkeys died within 160 days of STLV-III inoculation with a wasting syndrome, opportunistic infections, a primary retroviral encephalitis, and immunologic abnormalities including a decrease in T4+ peripheral blood lymphocytes. These data show that an immunodeficiency syndrome can be produced experimentally in a nonhuman primate by an agent from the HTLV-III/LAV group of retroviruses. The STLV-III-macaque system will thus provide a useful model for the study of antiviral agents and vaccine development for human AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Isolation of T-cell tropic HTLV-III-like retrovirus from macaques.

The isolation of a T-cell tropic retrovirus from three immunodeficient macaques and one macaque with lymphoma is described. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of acquired immune deficiency syndrome in humans (HTLV-III or LAV). This virus is referred to as simian T-lymphotropic virus type III (STLV-III) of macaques. The existence of a cytopathic, T-cell tropic virus resembling HTLV-III in monkeys may facilitate study of disease induction and vaccine development in an animal model.

Acquired Immunodeficiency Syndrome↗