Identification of a New Recipient in the Sydney Blood Bank Cohort: A Long-Term HIV Type 1-Infected Seroindeterminate Individual

Abstract

We have reported previously a cohort of long-term survivors of HIV-1 infection, known as the Sydney Blood Bank Cohort, who received HIV-1-positive blood from a common infected donor. A new recipient, C135, has been identified. This recipient became infected after receiving blood donated during the presumed time of seroconversion of the donor in February 1981. C135 has been infected for more than 18 years without signs of disease progression. The virus load in this recipient has remained below the detectable level (<20 RNA copies/ml of plasma) and repeated Western blot analyses have given an indeterminate result. By booster PCR techniques we have demonstrated that this individual is infected with HIV-1 and have characterized the viral nef and nef/LTR region sequences present. The strain of HIV-1 identified contains deletions of 88 bp from the nef alone region and a total of 139 bp deleted from the nef/LTR overlap and LTR regions. The LTR contains three wild-type Sp1 transcription factor-binding sites, the 3' wildtype NF-kappaB site, and a duplicated Sp1 and NF-kappaB region. A truncated Nef protein of only 19 amino acids is encoded. The deletions and rearrangements in the nef gene and LTR sequences are characteristic of Sydney Blood Bank Cohort strains of virus. The identification of C135 increases the Sydney Blood Bank Cohort size to nine individuals and represents a rare example of a genuine, long-term HIV-1 infection accompanied by indeterminate anti-HIV-1 serology.

Viral Phenotypes and Antibody Responses in Long-Term Survivors Infected with Attenuated Human Immunodeficiency Virus Type 1 Containing Deletions in thenefand Long Terminal Repeat Regions

“…Western blot and EIA analyses detected no gp120-specific antibodies for these individuals (data not shown). Subject C135 had not fully seroconverted on Western blots after more than 20 years of infection, extending previous findings (45). Total IgG responses for D36 and C98 waned after the commencement of antiretroviral therapy.…”

Characterization of Three nef -Defective Human Immunodeficiency Virus Type 1 Strains Associated with Long-Term Nonprogression

“…Peripheral blood mononuclear cells (PBMCs) were isolated from these venous blood samples using density gradient centrifugation on Ficoll-Hypaque. Washed PBMCs were resuspended and lysed at a concentration of 5 ϫ 10 6 to 10 ϫ 10 6 cells/ml in PCR lysis buffer (24). Viral loads were measured using the Amplicor HIV-1 monitor assay (Roche Molecular Systems, Branchburgh, N.J.).…”

“…Either amplimers were blunt ended, cloned, and sequenced or uncloned products were sequenced following amplification with primers containing M13 forward or M13 reverse tails as described previously (24). Sequences were aligned and analyzed using GeneWorks software (Oxford Molecular Group).…”

“…The largest study of LTS infected with a defective HIV-1 strain has been the Sydney Blood Bank Cohort (SBBC) identified in Australia (5,19,20,21,24). This cohort consists of eight individuals who became infected with a common nefdefective strain of virus after being transfused with blood products from a common donor.…”

Human Immunodeficiency Virus Type 1 Nef-Mediated Downregulation of CD4 Correlates with Nef Enhancement of Viral Pathogenesis

“…Nef, a 25-to 27-kDa regulatory protein encoded by human and simian immunodeficiency viruses, accelerates clinical progression to AIDS in humans infected with either human immunodeficiency virus type 1 (HIV-1) or HIV-2 and in rhesus macaques experimentally infected with simian immunodeficiency virus (SIV) (6,15,27,33,35,38,46,58,62,71). Similarly, Nef enhances the pathogenicity of HIV-1 in severe combined immunodeficiency (SCID) mice implanted with fragments of human fetal thymus and liver (SCID-hu Thy/Liv mice) (3,4,16,31).…”