nvestigation. The endogenous e pression of podoplanin on 293T cells plus the precise interaction of podoplanin with CLEC 2 raised the queries if podoplanin was incorpo rated into virions definitely developed in 293T cells, and if incorpo ration of podoplanin was required for CLEC 2 binding of these virions. Western blot examination and knock down of podoplanin e pression by shRNA presented affirmative answers to each issues Podoplanin depletion lowered CLEC 2, but not DC Sign, Nutlin-3a dependent HIV 1 transmis sion by B THP cells, and diminished transmission by platelets by about 50%. The latter locating is in agreement with our former observation that CLEC 2 certain antiserum lowered HIV 1 transmission by plate lets by about half.
Podoplanin for that reason joins the record of host variables which could be integrated to the HIV 1 envelope and affect HIV 1 infection by interacting with their cognate ligands. A prominent e ample for this kind of a factor is ICAM 1 which was identified for being incorpo rated to the viral membrane, and also to facilitate HIV 1 infection by binding to its ligand LFA 1 on T cells. The potential relevance https://en.wikipedia.org/wiki/IKK of podoplanin incorporation for HIV spread in contaminated folks is critically deter mined by the overlap of the podoplanin e pression pat tern with all the cellular tropism of HIV. Examination of T cell lines and PBMCs for podoplanin e pression yielded neg ative outcomes, at the very least when viable cells were ana lyzed, indicating that HIV particles created in individuals may not harbour podoplanin. The e ception may very well be viruses launched from kidney podocytes which have already been documented to e press podoplanin and also to be prone to HIV infection.
However, the biolog ical relevance of this approach is questionable. Within this con te t, furthermore, it demands for being mentioned that podoplanin e pression is up regulated in many tumours like Kaposi sar coma. Podoplanin CLEC 2 dependent platelet stimulation by tumour cells promotes hematogenous Nutlin-3a tumour metastasis, possibly by inducing growth issue secretion by platelets and by marketing formation of the platelet cap, which protects the tumour from mechanical forces. Consequently, podoplanin may possibly perform a role from the advancement in the AIDS related Kaposi sarcoma, but is unlikely to modulate HIV spread in sufferers.
somehow Nev ertheless, HIV 1 produced in PBMCs was transmitted to target cells inside a CLEC 2 dependent vogue, sug gesting that main T cells could possibly e press a up to now unrec ognized CLEC 2 ligand, that's integrated to the viral envelope and which facilitates HIV transmission by CLEC 2. Our ongoing scientific studies are devoted for the identification of this component. Podoplanin was not detected Nutlin-3a on viable CEM��174 cells and PBMCs, as established by our gat ing technique and by co staining together with the apoptosis and necrosis markers anne in V and 7 AAD, respectively. In contrast, Nutlin-3a we observed efficient reactivity of two various podoplanin antibodies with non viable cells, raising the intriguing possibility that podoplanin could be e pressed with the cell surface i