The more important is that difference of HIV-1 gp120, especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1β, which might supply a novel idea helping understand the pathogenesis of ADC.
Evidence implicating matrix metalloproteinases in the mechanism underlying accumulation of IL-1beta and neuronal apoptosis in the neocortex of HIV/gp120-exposed rats.
The more important is that difference of HIV-1 gp120, especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1β, which might supply a novel idea helping understand the pathogenesis of ADC.
The presence of the A allele at the TNF-alpha-308 site was overrepresented among adults with HIV dementia compared to those without dementia (0.28 vs 0.07; OR 5.5; 95% CI 1.8-17.0) and a healthy control population (0.28 vs 0.11).
The interactions between HIV-1- and CMV-infected macrophages and astrocytes lead to upregulation of TNF-alpha and IL-6 and enhancement of productive HIV-1 infection of macrophages and of 'restricted' HIV-1 infection of astrocytes with implications for the pathogenesis of AIDS dementia.
For example, concentration of TNF-alpha is increased in brain tissue of individuals who died with AIDS and correlates with the severity of AIDS Dementia Complex (ADC).
Tumor necrosis factor alpha (TNF-alpha) is a candidate human immunodeficiency virus type 1-induced neurotoxin that contributes to the pathogenesis of AIDS dementia complex.
In this study, we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex (ADC).
Astrocytes may be infected with the human immunodeficiency virus type 1 (HIV-1) or exposed to the HIV protein gp120, yet their role in the pathogenesis of HIV dementia is largely unknown.
HIV type 1 viral quasispecies were amplified by polymerase chain reaction (PCR) in the hypervariable V3 region of gp120 from six different regions of the brain (right and left frontal; right and left parietal; and right and left occipital) and from the peripheral blood mononuclear cells (PBMCs) of a patient who died of AIDS dementia complex (ADC).
Regions of sequence homology between gp120 and NLK may account for this inhibitory property of gp120 and functional interactions between gp120 and NLK may be important in the pathogenesis of the AIDS dementia complex.
Furthermore, while HIV+ subjects with ε 2 or ε 3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r= +0.35, p= 0.05), ε 4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r= -0.61, p= 0.02), had lower Global Cognitive Scores (r= -0.57, p= 0.03), and had poorer performance on tests involving learning (ε 4 allele x [APOE] interaction, p = 0.01).
There was no statistically significant correlation between risk of HIV dementia or HIV encephalitis in relation to apolipoprotein E genotypes, even after correction for length of survival with AIDS and antiretroviral treatment.