HL53738 - Christopher Hillyer - Emory University, Atlanta, GA
Anemia, granulocytopenia, lymphopenia, and thrombocytopenia are common in HIV infection though the pathogenesis of these abnormalities is not well understood. This study will conduct a comprehensive study of the site, function, and mechanism of the hematologic, virologic, and immunologic consequences of SIV infection in 12 rhesus monkeys (4 controls, 4 infected with a lymphocytotropic isolate, and 4 infected with a predominately monocytotropic isolate). This model will allow serial testing of animals (where time of infection is known) and study cell lineage specific SIV infection from in vivo infected samples.
This grant is being supported from 1996 to 2000.
This is a newly funded grant. Results are preliminary and have yet been published.
R01 HL43521 - Fred R. Kramer - Public Health Research Institute, New York, NY
Extremely sensitive assays are being developed by this investigator for detecting pathogenic human retroviruses. These assays will be used for screening donated blood and transplantable tissues in order to prevent the spread of T-lymphotropic leukemia/lymphoma and AIDS. The assays employ novel "binary" hybridization probes.
This grant is being supported from 1992 to 1999.
An attractive strategy for detecting rare infectious agents is to link a single-stranded oligonucleotide probe to a replicatable RNA that can be amplified exponentially after hybridization. The investigator has developed a novel implementation to this approach, in which the probe sequence is embedded within the sequence of a replicatable RNA. The resulting recombinant RNAs hybridize to nucleic acid targets as do ordinary probes, and the probe-target hybrids that they form are separated from nonhybridized probes as in ordinary sandwich hybridization assays. What make the recombinant-RNA probes unique is that they can then be amplified exponentially by incubation with the RNA-directed polymerase, QB replicase. As many as one billion copies of each replicatable probe can be synthesized in a single 30-minute incubation. The large number of copies that are synthesized can then be quantified by the incorporation of radioactive nucleotides or by the fluorescence of intercalating dyes. Since as little as a single molecule of replicatable RNA can initiate exponential amplification, these assays are potentially extraordinarily sensitive.