+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Negative elongation factor is required for the maintenance of proviral latency but does not induce promoter-proximal pausing of RNA polymerase II on the HIV long terminal repeat

, : Negative elongation factor is required for the maintenance of proviral latency but does not induce promoter-proximal pausing of RNA polymerase II on the HIV long terminal repeat. Molecular and Cellular Biology 34(11): 1911-1928

The role of the negative elongation factor (NELF) in maintaining HIV latency was investigated following small hairpin RNA (shRNA) knockdown of the NELF-E subunit, a condition that induced high levels of proviral transcription in latently infected Jurkat T cells. Chromatin immunoprecipitation (ChIP) assays showed that latent proviruses accumulate RNA polymerase II (RNAP II) on the 5' long terminal repeat (LTR) but not on the 3' LTR. NELF colocalizes with RNAP II, and its level increases following proviral induction. RNAP II pause sites on the HIV provirus were mapped to high resolution by ChIP with high-throughput sequencing (ChIP-Seq). Like cellular promoters, RNAP II accumulates at around position +30, but HIV also shows additional pausing at +90, which is immediately downstream of a transactivation response (TAR) element and other distal sites on the HIV LTR. Following NELF-E knockdown or tumor necrosis factor alpha (TNF-α) stimulation, promoter-proximal RNAP II levels increase up to 3-fold, and there is a dramatic increase in RNAP II levels within the HIV genome. These data support a kinetic model for proviral transcription based on continuous replacement of paused RNAP II during both latency and productive transcription. In contrast to most cellular genes, HIV is highly activated by the combined effects of NELF-E depletion and activation of initiation by TNF-α, suggesting that opportunities exist to selectively activate latent HIV proviruses.


PMID: 24636995

DOI: 10.1128/MCB.01013-13

Other references

Labenz, J.; Peitz, U.; Aygen, S.; Hennemann, O.; Stolte, M., 1997: Accuracy of rapid urease test and urea breath test for diagnosis of Helicobacter pylori infection after treatment An investigator-blind multicenter study. Gastroenterology 112(4 SUPPL ): A188

Bisits, A.M.; Smith, R.; Mesiano, S.; Yeo, G.; Kwek, K.; MacIntyre, D.; Chan, E.C., 2005: Inflammatory aetiology of human myometrial activation tested using directed graphs. There are three main hypotheses for the activation of the human uterus at labour: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from th...

Gabler, H., 1954: Seed pests of indigenous woody forest plants.. A short illustrated guide to identification and control for the practical forester, listing the more important insects, rodents and birds, and including a list of pests by woody plants attacked.

Schwibbe, Michael ., 1993: Annual Scientific Report of the German Primate Center DPZ. Primate Report. May; 36: 1-137

Zetterstrom, Rolf, 2006: The Nobel Prize in 2005 for the discovery of Helicobacter pylori: Implications for child health. The Nobel Prize in Physiology or Medicine in 2005 has been awarded to B. Marshall and R. Warren for their discovery that peptic ulcer disease is caused by an infection with Helicobacter pylori. This infection, which affects about half of the world...

Amineh, R.K.; Eleftheriades, G.V., 2013: 2D and 3D sub-diffraction source imaging with a superoscillatory filter. In this paper, we propose an approach to overcome the well-known "diffraction limit" when imaging sources several wavelengths away. We employ superdirectivity antenna concepts to design a well-controlled superoscillatory filter (SOF) bas...

Koch, W.C.; Barnstein, B.; Harger, J.H., 1997: Natural history of congenital parvovirus B19 infection Factors affecting intrauterine transmission. Pediatric Research 41(4 PART 2): 124A

Anonymous, 1967: Round table discussion on mycotoxins. Annali Dell'istituto Superiore di Sanita 3(3): 327-357

Astle, A.T.; Blighe, A.J.; Webb, B.S.; McGraw, P.V., 2016: The effect of normal aging and age-related macular degeneration on perceptual learning. We investigated whether perceptual learning could be used to improve peripheral word identification speed. The relationship between the magnitude of learning and age was established in normal participants to determine whether perceptual learning e...

Cohen, R.; Berkovic, G., 1994: Creation of second-order nonlinearity in polymers by light-induced asymmetric charge injection. A new method for creating and enhancing second-order optical nonlinearity in polymer-dye films by asymmetric photoinjection of electric charges is introduced. The samples are composed of two separate layers, an organic photoconductor that generate...