Abstract:
:The human protein apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamination takes place after virus entry into target cells, APOBEC3G function is dependent on its association with the viral nucleoprotein complexes that synthesize cDNA and must therefore be incorporated into virions as they assemble in infected cells. Here we show that the HIV-1 virion infectivity factor (Vif) protein protects the virus from APOBEC3G-mediated inactivation by preventing its incorporation into progeny virions, thus allowing the ensuing infection to proceed without DNA deamination. In addition to helping exclude APOBEC3G from nascent virions, Vif also removes APOBEC3G from virus-producing cells by inducing its ubiquitination and subsequent degradation by the proteasome. Our findings indicate that pharmacologic strategies aimed at stabilizing APOBEC3G in HIV-1 infected cells should be explored as potential HIV/AIDS therapeutics.
journal_name
Nat Medjournal_title
Nature medicineauthors
Sheehy AM,Gaddis NC,Malim MHdoi
10.1038/nm945keywords:
subject
Has Abstractpub_date
2003-11-01 00:00:00pages
1404-7issue
11eissn
1078-8956issn
1546-170Xpii
nm945journal_volume
9pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::We investigated whether immunization with recombinant anti-idiotypic antibody fragments mimicking the conformation of the capsular antigen can protect against infection by group B streptococcus, an important neonatal pathogen. Single-chain fragment-variable anti-idiotypes competed with the type III carbohydrate for bi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0698-705
更新日期:1998-06-01 00:00:00
abstract::Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. T...
journal_title:Nature medicine
pub_type: 杂志文章,随机对照试验
doi:10.1038/s41591-020-0801-z
更新日期:2020-04-01 00:00:00
abstract::Cancer-specific cell-surface antigens are ideal targets for monoclonal antibody (mAb)-based immunotherapy but are likely to have previously been identified in transcriptome or proteome analyses. Here, we show that the active conformer of an integrin can serve as a specific therapeutic target for multiple myeloma (MM)....
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4431
更新日期:2017-12-01 00:00:00
abstract::Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3246
更新日期:2013-08-01 00:00:00
abstract::Preventing the immune escape of tumor cells by blocking inhibitory checkpoints, such as the interaction between programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) receptor, is a powerful anticancer approach. However, many patients do not respond to checkpoint blockade. Tumor PD-L1 expression is a potentia...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0217-1
更新日期:2018-12-01 00:00:00
abstract::Pten is an important phosphatase, suppressing the phosphatidylinositol-3 kinase/Akt pathway. Here, we generated adipose-specific Pten-deficient (AdipoPten-KO) mice, using newly generated Acdc promoter-driven Cre transgenic mice. AdipoPten-KO mice showed lower body and adipose tissue weights despite hyperphagia and enh...
journal_title:Nature medicine
pub_type: 杂志文章,收录出版
doi:10.1038/nm1117
更新日期:2004-11-01 00:00:00
abstract::Severe malaria is a major cause of childhood mortality in sub-Saharan Africa but the factors predisposing children to severe forms of malaria have not been fully elucidated. In a case-control study of over 1,200 Gambian children hepatitis B virus carriage was significantly increased amongst cases of severe malaria com...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0495-374
更新日期:1995-04-01 00:00:00
abstract::Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcgamma1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcgamma-Fel d1 protein induced dose-d...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1219
更新日期:2005-04-01 00:00:00
abstract::Programmed cell death (apoptosis) seems to be the principal mechanism whereby anti-oncogenic therapies such as chemotherapy and radiation effect their responses. Resistance to apoptosis, therefore, is probably a principal mechanism whereby tumors are able to overcome these cancer therapies. The transcription factor NF...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/7410
更新日期:1999-04-01 00:00:00
abstract::Massive release of tumor necrosis factor is responsible for the potentially fatal larisch-Herxheimer reaction that follows antibiotic treatment of relapsing fever due to Borrelia recurrentis. We have undertaken the quantitative purification of the components of B. recurrentis that stimulate human monocytes to produce ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/4007
更新日期:1998-12-01 00:00:00
abstract::A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepatocytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0398-285
更新日期:1998-03-01 00:00:00
abstract::Drug-induced liver injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market; this is partially due to the inability to identify patients who are at risk1. In this study, we developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-1023-0
更新日期:2020-10-01 00:00:00
abstract::In the nervous system, NMDA receptors (NMDARs) participate in neurotransmission and modulate the viability of neurons. In contrast, little is known about the role of NMDARs in pancreatic islets and the insulin-secreting beta cells whose functional impairment contributes to diabetes mellitus. Here we found that inhibit...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3822
更新日期:2015-04-01 00:00:00
abstract::Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically lin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3932
更新日期:2015-10-01 00:00:00
abstract::Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mec...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3514
更新日期:2014-05-01 00:00:00
abstract::The glycosylation of the circulating immunoglobulin-gamma (IgG) antibody molecules changes in rheumatoid arthritis. The extent of the changes correlates with the disease severity and reverses in remission. We demonstrate here that the alteration in glycosylation associated with rheumatoid arthritis can create a new mo...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0395-237
更新日期:1995-03-01 00:00:00
abstract::Temperatures that deviate from the long-term local norm affect human health, and are projected to become more frequent as the global climate changes1. There are limited data on how such anomalies affect deaths from injuries. In the present study, we used data on mortality and temperature over 38 years (1980-2017) in t...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0721-y
更新日期:2020-01-01 00:00:00
abstract::In the version of this article originally published, there was an error in the legend for Extended Data Fig. 7. The legend for panel f was originally: "f, FACS analysis of IL7R-, CD62L- and CD45RA- expression on TRAC-1928ζ and TRAC-1XX CAR T cells at day 63 post CAR infusion (representative for at least n = 3 mice per...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-019-0360-3
更新日期:2019-03-01 00:00:00
abstract::The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/9473
更新日期:1999-06-01 00:00:00
abstract::Proper function of the endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states, including metabolic diseases. Although the ER and mitochondria play distinct cellular roles, these organelles also form physical interacti...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3735
更新日期:2014-12-01 00:00:00
abstract::Obesity and metabolic syndrome are increasingly recognized as major risk factors for cardiovascular disease. Herein we show that Krüppel-like transcription factor 5 (KLF5) is a crucial regulator of energy metabolism. Klf5(+/-) mice were resistant to high fat-induced obesity, hypercholesterolemia and glucose intoleranc...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1756
更新日期:2008-06-01 00:00:00
abstract::Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting pr...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3048
更新日期:2013-02-01 00:00:00
abstract::To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and m...
journal_title:Nature medicine
pub_type: 临床试验,杂志文章
doi:10.1038/nm.2006
更新日期:2009-08-01 00:00:00
abstract::Our understanding of Alzheimer's disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly ass...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-0815-6
更新日期:2020-05-01 00:00:00
abstract::Much has been written about the advantages and disadvantages of various oncology model systems, with the overall finding that these models lack the predictive power required to translate preclinical efficacy into clinical activity. Despite assertions that some preclinical model systems are superior to others, no singl...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3853
更新日期:2015-05-01 00:00:00
abstract::Treatment for schistosomiasis, which is responsible for more than 280,000 deaths annually, depends almost exclusively on praziquantel. Millions of people are treated annually with praziquantel, and drug-resistant parasites thus are likely to evolve. Phosphinic amides and oxadiazole 2-oxides, identified from a quantita...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1737
更新日期:2008-04-01 00:00:00
abstract::Synthetic vascular prostheses are foreign bodies, so that blood coagulation can occur on their luminal surfaces, causing graft occlusion very frequently in prostheses of small diameter. A vascular prosthesis needs angiogenesis for endothelialization of the luminal surface, as endothelial cells have natural and permane...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0196-90
更新日期:1996-01-01 00:00:00
abstract::Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal r...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm877
更新日期:2003-06-01 00:00:00
abstract::Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease. This symptom is also frequently reported in patients receiving angiotensin-converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension, although the underlying mechanism is u...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0796-814
更新日期:1996-07-01 00:00:00
abstract::The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essenti...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/81380
更新日期:2000-11-01 00:00:00