Journal Of Virology Reports On Link Between HIV and Niemann Pick Cholesterol Gene: Intact Intracellular Cholesterol Trafficking Pathways Mediated by NPC1 are Needed for Efficient HIV-1 Production
June 5, 2009 by Chris Hempel
Filed under News
Journal of Virology
May 27, 2009
Deficiency of Niemann-Pick type C-1 Protein Impairs HIV-1 Release and Results in Gag Accumulation in Late Endosomal/Lysosomal Compartments
Tang Y, Leao IC, Coleman EM, Broughton RS, Hildreth JE.
Human immunodeficiency virus type 1 (HIV-1) relies on cholesterol-laden lipid raft membrane microdomains for entry into and egress out of susceptible cells. In the present study, we examine the need for intracellular cholesterol trafficking pathways with respect to HIV-1 biogenesis using Niemann-Pick type C1 deficient cells (NPCD) wherein these pathways are severely compromised, causing massive accumulation of cholesterol in late endosomal/lysosomal (LE/L) compartments.
We have found that induction of an NPC disease-like phenotype through treatment of various cell types with the commonly-used hydrophobic amine drug U18666A resulted in profound suppression of HIV-1 release.
Further, NPCD EBV-transformed B lymphocytes and fibroblasts from patients with NPC disease infected with a CD4-independent strain of HIV-1 or transfected with an HIV-1 proviral clone, respectively, replicated HIV-1 poorly when compared to normal cells.
Infection of the NPCD fibroblasts with a VSV-G pseudotyped strain of HIV-1 produced similar results, suggesting a post-entry block to HIV-1 replication in these cells. Examination of these cells using confocal microscopy showed an accumulation and stabilization of Gag in LE/L compartments. Additionally, normal HIV-1 production could be restored in NPCD cells upon expression of a functional NPC1 protein, and overexpression of NPC1 increased HIV-1 release.
Taken together, our findings demonstrate that intact intracellular cholesterol trafficking pathways mediated by NPC1 are needed for efficient HIV-1 production.
Can I simply just say what a relief to uncover somebody who
genuinely knows what they are talking about on the net.
You actually realize how to bring an issue to light and make it important.
More people really need to read this and understand this side of the story.
It’s surprising you are not more popular because you certainly have the gift.
私のちんぽこは若いの頃知能が無いためにかなり何度も何度も自慰行為をしてしまったせいでさきっぽが短小のままで、皮かむりを維持したままになってしまったのです。ちんぽこが長さが伸びたのが良かったのでチンコが硬くなったように思います。真性包茎の気まずさはオペをしなければならない事態になると見たことがあるので大喜びでした。私自身も包茎なのではと不思議に思っていましたが、知人と比較してもアダルトビデオを見ても確実に小さいんだという事が判明しました。
When you experience this problem with your modules check
the rear connector as your first point in the troubleshooting process.
Here you can get step by step guidance on how to repair most of the makes
in the vehicle market. Fortunately there are a few companies that
can provide Quality M3001A repairs at highly competitive prices.
Et sur ce point nous ne transigeons pas, en ne comparant que de facon independante, pour que cet achat
ne soit pas de l’argent jete par les fenetres.
Although Yahoo isn’t the biggest, or the highest ranking search engine on the internet, it is
still one of the most essential, and if you want
use search engine optimization and promotion as a main technique
in your marketing arsenal, you unquestionably need to get listed here.
The usual SEO methods include keyword research, link building
and such. Unlike TV, radio and other traditional marketing channels that need
big budgets to be effective, SEO can be cost
effective. Further the sites whose ranking using the search engines is good will attract potential clients, which results to mores sales.