ABSTRACT
The authors studied the transcriptional activity of blood-and cerebrospinal fluid (CSF)-derived nef/long-terminal repeat (LTR) sequences isolated from a slow progressor infected with nef-deleted human immunodeficiency virus type 1 (HIV-1) who developed HIV-associated dementia (HIVD). The transcriptional activity of CSF-derived nef/LTR clones isolated during HIVD was up to 4.5-fold higher than blood-derived clones isolated before and during HIVD when tested under basal, phorbol 12-myristate 13-acetate-(PMA-), and Tat-activated conditions, and was associated with the presence of duplicated nuclear factor (NF)-kappaB and specificity factor-1 (Sp-1) binding sites coupled with a truncated nef sequence, increased replication capacity, and high CSF viral load. Thus, nef and LTR mutations that augment transcription may contribute to neuropathogenesis of nef-deleted HIV-1.
Subject(s)
AIDS Dementia Complex/virology , Gene Products, nef/genetics , HIV Long Terminal Repeat/genetics , HIV-1/genetics , Transcriptional Activation , Gene Deletion , Gene Expression Regulation, Viral , Gene Products, nef/blood , Gene Products, nef/cerebrospinal fluid , Gene Products, tat/genetics , HIV-1/pathogenicity , Humans , Viral Load , Virulence , nef Gene Products, Human Immunodeficiency Virus , tat Gene Products, Human Immunodeficiency VirusABSTRACT
In determining levels of expression of HIV-1 Nef protein within the central nervous system (CNS) we assessed antibody responses to the protein both peripherally and in CNS. Antibodies to Nef were not detected within the CNS despite detection of antibodies to both gp41 and Nef in peripheral blood and representative virus isolates derived from CNS and peripheral blood (PB) samples containing full length nef sequence and virus-infected cells expressing Nef protein. We conclude from this that expression of Nef within the CNS is such that little or no antibody production occurs and that these differences indicate that Nef protein may not be directly contributing to the AIDS dementia complex. Expression of Nef protein in PHA-activated peripheral blood mononuclear cells from CNS derived isolates was different to that of coincidental PB derived isolates in that partial surface expression was observed for the latter. The results suggest that antigenic presentation of Nef within the CNS is anomalous and that Nef protein expression, at least for the limited number of in vitro derived isolates tested, has a different localization pattern.
