Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. October 6-11, 1991, Padova/Venice, Italy, p. 104, 1991.. Unique Identifier : AIDSLINE ICDB/92682442 Wong PK; Shikoval E; Lin YC; Aaha K; Szurek PF; Madden R; Brooks BR; UT M.D. Anderson Cancer Center, Science Park-Res. Div.,; Smithville, TX 78957
Abstract:
The ts1 mutant of Moloney murine leukemia virus TB causes a degenerative neurologic and immunologic disease in mice, characterized by development of spongiform encephalomyelopathy resulting in hindlimb paralysis, marked thymic atrophy associated with immunodeficiency and general bodywasting. T cells, particularly CD4+ helper T cells, play a key role in the pathogenesis of the disease induced by ts1. ts1 is, therefore, unique among the described murine retroviruses in its ability to afflict both the CNS and the T-cell compartment of the immune system in the same host. This particular duality in causing degenerative diseases involving both the CNS and immune system is shared by the lentiviruses responsible for development of the acquired immunodeficiency syndrome (AIDS) of man and macaque. Our goal has been to elucidate the specific cellular and molecular mechanisms that underlie this neuro- and immunopathogenicity of ts1. We have previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-Ile, in the precursor envelope protein gPr80env. It was further shown that at the restrictive temperature the Val-25-Ile substitution did not prevent oligomerization of the gPr80env proteins; however, the structure of the oligomer was incompetent for transport from the ER to the Golgi. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to accumulation of the gPr80env oligomers in the ER. Since glial cells and neurons may be a target of ts1 infection, in vivo primary astrocytic cultures were established and the cytopathic effect of ts1 and MoMuLV-TB on these cells assessed. Our results show that both viruses replicate well in astrocytes and that their replication is cytopathic, albeit to different degrees. ts1 appears to produce greater killing than the wild-type virus. Furthermore, it was found that the rate of processing of gPr80env of ts1 appears to correlate with its cytopathic effect in these cells. Electron microscopic studies of the ts1-infected astrocytes revealed large numbers of aberrant particles in the ER. The in vitro cytopathic effect of ts1 on astrocytes may reflect what happens in vivo.
Keywords: Animal Central Nervous System Diseases/*ETIOLOGY/PATHOLOGY Cytopathogenic Effect, Viral Gene Products, env Leukemia, Experimental/*COMPLICATIONS/PATHOLOGY Moloney Leukemia Virus/PHYSIOLOGY Virus Replication ABSTRACT 920930
M9290913
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
