The Macfarlane Burnet Centre for Medical Research Limited

Australian Red Cross Society

Dale Alan McPhee

Nicholas John Deacon

Suzanne Crowe

Jennifer Catherine Learmont

David Cooper

The present invention is directed toward immunologic- and nucleic acid-based methodologies for the detection of non-pathogenic human immunodeficiency virus type 1 (HIV-1) strains in the body fluids of HIV-infected individuals. A blood donor infected with HIV-1 and a cohort of six blood or blood product recipients infected from this donor were studied. These patients, who remained free of HIV-1-related disease and displayed stable and normal CD4 lymphocyte counts 10 to 14 years after infection, were termed long-term nonprogressors (LTNPs). The molecular characterization of HIV-1 sequences obtained from either virus isolates or patient peripheral blood mononuclear cells (PBMCs) of LTNPs identified similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the long terminal repeat (LTR). These deletions corresponded to amino acids 166-206, or nucleotides 9281 to 9437, of the HIV-1.sub.NL43 nef/LTR region. Methods were developed to detect the presence of nonpathogenic HIV-1 strains carrying these deletions in HIV-infected patients.

Methods for the detection of non-pathogenic HIV-1 strains containing

This invention is directed toward non-pathogenic human immunodeficiency virus type 1 (HIV-1) strains containing deletions in the nef gene and U3 region of the long terminal repeat (LTR). A blood donor infected with HIV-1 and a cohort of six blood or blood product recipients infected from this donor were identified. These individuals, who remained free of HIV-1-related disease with stable and normal CD4.sup.+ lymphocyte counts 10 to 14 years after infection, were termed long-term nonprogressors (LTNPs). The molecular characterization of HIV-1 sequences obtained from either virus isolates or patient peripheral blood mononuclear cells (PBMCs) of LTNPs identified similar deletions in the nef gene and in the region of overlap of nef and the U3 region of the LTR. Full-length sequencing of one isolate genome and amplification of selected HIV-1 genome regions from other cohort members revealed no other abnormalities of obvious functional significance. These deletions corresponded to amino acids 166-206, or nucleotides 9281 to 9437, of the HIV-1.sub.NL43 nef/LTR region. These data illustrate the importance of nef or the U3 region of the LTR in determining the pathogenicity of HIV-1. These non-pathogenic strains should prove useful, inter alia, in the development of HIV-1-specific diagnostic reagents.

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Fitzroy, Australia

Dale Alan McPhee