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Biomedical subjects

A Spinner

Publications and source records attributed to A Spinner.

7 recordsLinked to original sources

T-cell lymphoproliferative disorder in an aged rhesus macaque.

A CD8+ T-cell leukemia was diagnosed in an aged female rhesus macaque. Although leukemia and lymphoma in nonhuman primates are commonly associated with simian T-lymphotropic virus, gibbon ape leukemia virus, oncogenic herpesviruses, and types C, D, and E retroviruses, this monkey was not infected with any of these viruses. However, the monkey did have antibodies against herpesvirus saimiri. This likely represents cross-reactivity of the herpesvirus saimiri assay with rhesus monkey rhadinovirus (RRV) antibodies; RRV was first described in rhesus macaques that were identified as having antibodies against herpesvirus saimiri. Rhesus rhadinovirus is a gamma herpesvirus, related antigenically to herpesvirus saimiri and Kaposi's sarcoma-associated herpesvirus (KSHV), which have been linked to lymphoproliferative disorders in primates and humans, respectively. Moreover, an oncogene has been recently identified in the RRV genome that is equivalent in position to the herpesvirus saimiri and KSHV oncogenes. Presently, the association of RRV infection with disease in nonhuman primates is unknown.

Age Factors↗

9-[2-(Phosphonomethoxy)propyl]adenine therapy of established simian immunodeficiency virus infection in infant rhesus macaques.

The long-term therapeutic and toxic effects of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) were evaluated in simian immunodeficiency virus (SIV)-infected newborn rhesus macaques. Four untreated SIV-infected newborn macaques developed persistently high levels of viremia, and three of the four animals had rapidly fatal disease within 3 months. In contrast, long-term PMPA treatment of four newborn macaques starting 3 weeks after virus inoculation resulted in a rapid, pronounced, and persistent reduction of viremia in three of the four animals. Emergence of virus with fivefold-decreased susceptibility to PMPA occurred in all four PMPA-treated animals and was associated with the development of a lysine-to-arginine substitution at amino acid 65 (K65R mutation) and additional mutations in the reverse transcriptase; however, the clinical implications of this low-level drug resistance are nuclear. No toxic side effects have been seen, and all PMPA-treated animals have remained disease-free for more than 13 months. Our data suggest that PMPA holds much promise for the treatment of human immunodeficiency virus-infected human infants and adults.

Adenine↗

Asymptomatic infection of the central nervous system by the macaque immunosuppressive type D retrovirus, SRV-1.

The aetiological agent of spontaneously occurring simian acquired immune deficiency syndrome (SAIDS) in rhesus monkeys (Macaca mulatta) at the California Primate Research Center is a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). SRV-1 DNA and RNA have previously been detected in the brains of rhesus monkeys with SAIDS in the absence of viral antigen or neuropathological lesions. In this study we further define the relationship between SRV-1 and the central nervous system (CNS) in rhesus monkeys by examining the CNS for infectious SRV-1, viral antigen and anti-SRV-1 antibodies. In addition, cerebrospinal fluid (CSF) was assayed for alterations in IgG and albumin levels, IgG/albumin ratios and cell count in comparison to uninfected control animals. No differences in CSF parameters were detected between infected and uninfected animals except for the presence of infectious SRV-1 which was isolated from the CSF from 13 out of 19 (68%) viraemic rhesus monkeys. The probable source of this virus was the choroid plexus, where approximately 1 in 1000 surface epithelial cells were found to contain viral antigen by immunohistochemistry. Antibodies against SRV-1 were not detected in the CSF even when present in the serum. Neither infectious virus nor viral antigen were found in the brain parenchyma of any animal examined. Thus infection of the CNS by SRV-1 appears to be subclinical without an intrathecal immune response. This may be related to the apparent restriction of productive infection in the CNS to cells of the choroid plexus.

Albumins↗

Simian AIDS ELISA: sensitivity, specificity and predictive values based on a comparison with Western blot technique.

Simian Acquired Immunodeficiency Syndrome (SAIDS) is an important disease in captive primates in the United States associated with an unusually high mortality rate. Isolation of a type D retrovirus as the cause of SAIDS was rapidly followed by the development of an enzyme linked immunosorbent assay (ELISA) to determine the exposure of rhesus macaques (Macaca mulatta) to this virus. With increased use of the ELISA, a better understanding for interpretation of results was needed. One hundred thirty-one rhesus macaques were tested for the presence of antibody against SAIDS type D retrovirus (SRV) by both ELISA and Western blot techniques. Sensitivity, specificity and predictive values for the SAIDS ELISA were calculated for two populations based on a comparison with Western blot results. Sera was tested from two distinct populations, an endemic and a control population. Seventy-one macaques from a half-acre outdoor corral where SAIDS was first recognized made up the endemic population. Sixty rhesus macaques from both indoor and outdoor areas where the disease was not recognized made up the control population. This study has shown the ELISA to be a useful screening tool based on its high sensitivity for both endemic and control populations. This screening method provides a rapid and economical way to diagnose and manage SAIDS in captive non-human primate colonies.

Animals↗

Hematologic abnormalities in simian acquired immune deficiency syndrome.

Hematologic abnormalities were defined in 31 rhesus monkeys (Macaca mulatta) with simian acquired immune deficiency syndrome (SAIDS). Animals manifested anemia (hypochromic/microcytic), severe neutropenia and progressive lymphopenia, monocytosis and occasional thrombocytopenia. Bone marrow studies showed erythroid hyperplasia with a marked left shift and adequate megakaryocytes. Two animals showed profound hypoplasia of all hematopoietic elements. Most animals were iron deficient, but the course of the anemia suggested additional factors. There was no evidence of immune hemolysis. The pathogenesis of these abnormalities is not clear and will require further study. This reproducible disease will allow studies to elucidate the mechanisms of viral-induced hematologic abnormalities.

Acquired Immunodeficiency Syndrome↗

Pathogenesis of simian AIDS in rhesus macaques inoculated with the SRV-1 strain of type D retrovirus.

Type D retrovirus was isolated from rhesus macaques with simian acquired immunodeficiency syndrome (SAIDS) and transmitted to healthy rhesus macaques with tissue culture medium containing the virus. The clinical, immunologic, and lymph node morphologic changes were observed in 9 rhesus macaques for 52 weeks after inoculation. A spectrum of clinical signs developed including early death, persistent SAIDS, and apparent remission. Animals that died or developed persistent SAIDS had characteristic lymphoid depletion, persistently depressed peripheral blood mononuclear cell (PBMC) mitogenic response, and decreased serum immunoglobulins. The SAIDS retrovirus (SRV) was recovered from PBMC of 8 of the animals after inoculation. Virus could not be recovered from PBMC of one animal in remission, but this animal developed serum-neutralizing antibodies to SRV after inoculation. Seven of the animals seroconverted to SRV after inoculation, all 9 were seronegative for human T-lymphotropic virus-III, and 5 animals tested were seronegative to human T-lymphotropic virus-I. These findings support the etiologic role of the type D retrovirus in SAIDS and further define the pathogenesis of this disease.

Acquired Immunodeficiency Syndrome↗