the-test-rapid-cell-free-cd4-enumeration-using-whole-saliva

The &alpha;-test: Rapid Cell-free CD4 Enumeration Using Whole Saliva

There is an urgent need for affordable CD4 enumeration to monitor HIV disease. CD4 enumeration is out of reach in resource-limited regions due to the time ...

Weill Cornell Medical College 

To identify positive or negative factors for HIV-1 infectivity, clones from the U937 promonocytic cell line that express similar levels of CD4 and CXCR4, but differ in HIV-1 susceptibility, were compared. In contrast to HIV-1 permissive clone 10 (plus), nonpermissive clone 17 (minus) was adherent to coverslips coated with chemokines, was phagocytic, killed bacteria, and expressed human leukocyte elastase (HLE) in a granule-like compartment (HLEG) that was never detected at the cell surface (HLECS). In contrast to the minus clone, the plus clone expressed HLE on the cell surface and was adherent to coverslips coated with the HLECS ligands alpha1proteinase inhibitor (alpha1PI, alpha1antitrypsin) and the HIV-1 fusion peptide. The phosphorylation status of several important signaling proteins was studied at the single cell level. Tumor suppressor p53, NF-kappaB p65, and Akt were constitutively phosphorylated in the plus clone, but not in the minus clone. Surprisingly, both alpha1PI and LPS induced phosphorylation of NF-kappaB p65 Ser-536 in both clones, but induced dephosphorylation of Ser-529 in the plus clone only. HIV-1 permissivity was conferred to the minus clone in a manner that required stimulation by both alpha1PI and LPS and was coincident to NF-kappaB p65 phosphorylation/dephosphorylation events as well as translocation of HLE to the cell surface. Even when stimulated, the minus clone exhibited greater reverse transcriptase activity, but less p24, than the plus clone. Results presented suggest that HIV-1 uptake and production efficiency are influenced by signaling profiles, receptor distribution, and the phagocytic capacity specific to the stage of differentiation of the CD4+ target cell.

Article	Year
Blood\| PubMed ID: 12933574	2003
NF-kappaB signaling, elastase localization, and phagocytosis differ in HIV-1 permissive and nonpermissive U937 clones. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 18097051	2008
PloS one\| PubMed ID: 22363634	2012

Cynthia L. Bristow

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