Abstract:
:Nullbasic is a mutant form of the HIV-1 transcriptional activator protein (Tat) that strongly inhibits HIV-1 transcription and replication in lymphocytes in vitro To investigate Nullbasic inhibition in vivo, we employed an NSG mouse model where animals were engrafted with primary human CD4+ cells expressing a Nullbasic-ZsGreen1 (NB-ZSG) fusion protein or ZSG. NB-ZSG and ZSG were delivered by using a retroviral vector where CD4+ cells were transduced either prior to (preinfection) or following (postinfection) HIV-1 infection. The transduced cells were analyzed in vitro up to 10 days postinfection (dpi) and in vivo up to 39 dpi. Compared to ZSG, NB-ZSG strongly inhibited HIV-1 replication both in vitro and in vivo using preinfection treatment. In vitro, HIV-1 mRNA levels in cells were reduced by up to 60-fold. In vivo, HIV-1 RNA was undetectable in plasma samples during the course of the experiment, and HIV-1 mRNA levels in resident CD4+ cells in organ tissue were reduced up to 2,800-fold. Postinfection treatment of HIV-1-infected cells with NB-ZSG attenuated HIV-1 infection for up to 14 days. In vitro, a 25-fold reduction of viral mRNA in cells was observed but diminished to a <2-fold reduction by 10 dpi. In vivo, HIV-1 RNA was undetectable in plasma of NB-ZSG mice at 14 dpi but afterwards was not significantly different between NB-ZSG mice and control mice. However, we observed higher levels of CD4+ cells in NB-ZSG mice than in control mice, suggesting that NB-ZSG imparted a survival advantage to HIV-1-infected animals.IMPORTANCE HIV-1 infection is effectively controlled by antiviral therapy that inhibits virus replication and reduces viral loads below detectable levels in patients. However, therapy interruption leads to viral rebound due to latently infected cells, which serve as a source of continued viral infection. Interest in strategies leading to a functional cure for HIV-1 infection by long-term or permanent viral suppression is growing. Here, we show that a mutant form of the HIV-1 Tat protein, referred to as Nullbasic, inhibits HIV-1 transcription in infected CD4+ cells in vivo Analysis shows that stable expression of Nullbasic in CD4+ cells could lead to durable anti-HIV-1 activity. Nullbasic, as a gene therapy candidate, could be a part of a functional-cure strategy to suppress HIV-1 transcription and replication.
journal_name
mBiojournal_title
mBioauthors
Jin H,Sun Y,Li D,Lin MH,Lor M,Rustanti L,Harrich Ddoi
10.1128/mBio.01769-19subject
Has Abstractpub_date
2019-08-27 00:00:00issue
4issn
2150-7511pii
mBio.01769-19journal_volume
10pub_type
杂志文章相关文献
mBio文献大全abstract::Nutritional immunity is an elegant host mechanism used to starve invading pathogens of necessary nutrient metals. Calprotectin, a metal-binding protein, is produced abundantly by neutrophils and is found in high concentrations within inflammatory sites during infection. Group B Streptococcus (GBS) colonizes the gastro...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02302-20
更新日期:2020-11-10 00:00:00
abstract::Production of metallo-β-lactamases (MBLs), which hydrolyze carbapenems, is a cause of carbapenem resistance in Enterobacteriaceae Development of effective inhibitors for MBLs is one approach to restore carbapenem efficacy in carbapenem-resistant Enterobacteriaceae (CRE). We report here that sulfamoyl heteroarylcarboxy...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03144-19
更新日期:2020-03-17 00:00:00
abstract::Murein lipoprotein (Lpp) and peptidoglycan-associated lipoprotein (Pal) are major outer membrane lipoproteins in Escherichia coli Their roles in cell-envelope integrity have been documented in E. coli laboratory strains, and while Lpp has been linked to serum resistance in vitro, the underlying mechanism has not been ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00603-17
更新日期:2017-05-23 00:00:00
abstract::In contrast to usual laboratory conditions, most bacteria in the human body grow in biofilms. Encased in a structured matrix, many pathogens display heightened resistance to antibiotics. Pseudomonas aeruginosa lung infections in cystic fibrosis patients represent a prime example of the clinical challenges that antibio...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.00061-12
更新日期:2012-04-03 00:00:00
abstract:UNLABELLED:Despite long-term investment, influenza continues to be a significant worldwide problem. The cornerstone of protection remains vaccination, and approved vaccines seek to elicit a hemagglutination inhibition (HAI) titer of ≥1:40 as the primary correlate of protection. However, recent poor vaccine performance ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00417-16
更新日期:2016-04-19 00:00:00
abstract::Resistance-nodulation-division (RND) superfamily efflux systems have been widely studied for their role in antibiotic resistance, but their native biological functions remain poorly understood. We previously showed that loss of RND-mediated efflux in Vibrio cholerae resulted in activation of the Cpx two-component regu...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00126-17
更新日期:2017-05-16 00:00:00
abstract:UNLABELLED:The increasing antibiotic resistance of pathogenic Escherichia coli species and the absence of a pan-protective vaccine pose major health concerns. We recently identified, by subtractive reverse vaccinology, nine Escherichia coli antigens that protect mice from sepsis. In this study, we characterized one of ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00010-12
更新日期:2012-04-10 00:00:00
abstract:UNLABELLED:The strong restriction barrier present in Staphylococcus aureus and Staphylococcus epidermidis has limited functional genomic analysis to a small subset of strains that are amenable to genetic manipulation. Recently, a conserved type IV restriction system termed SauUSI (which specifically recognizes cytosine...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00277-11
更新日期:2012-03-20 00:00:00
abstract::Glycoprotein B (gB), gD, and gH/gL constitute the fusion machinery of herpes simplex virus (HSV). Prior studies indicated that fusion occurs in a stepwise fashion whereby the gD/receptor complex activates the entire process, while gH/gL regulates the fusion reaction carried out by gB. Trimeric gB is a class III fusion...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00429-12
更新日期:2012-11-20 00:00:00
abstract::In immunocompromised hosts, latent infection with Toxoplasma gondii can reactivate from tissue cysts, leading to encephalitis. A characteristic of T. gondii bradyzoites in tissue cysts is the presence of amylopectin granules. The regulatory mechanisms and role of amylopectin accumulation in this organism are not fully...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01289-17
更新日期:2017-08-29 00:00:00
abstract:UNLABELLED:Protein-protein interactions are important for virtually every biological process, and a number of elegant approaches have been designed to detect and evaluate such interactions. However, few of these methods allow the detection of dynamic and real-time protein-protein interactions in bacteria. Here we descr...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01050-14
更新日期:2014-05-20 00:00:00
abstract::Members of the genus Mycobacterium are the most prevalent cause of infectious diseases. Mycobacteria have a complex cell envelope containing a peptidoglycan layer and an additional arabinogalactan polymer to which a mycolic acid bilayer is linked; this complex, multilayered cell wall composition (mAGP) is conserved am...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02213-16
更新日期:2017-02-07 00:00:00
abstract::The diversity of the genetic code systems used by microbes on earth is yet to be elucidated. It is known that certain methanogenic archaea employ an alternative system for cysteine (Cys) biosynthesis and encoding; tRNACys is first acylated with phosphoserine (Sep) by O-phosphoseryl-tRNA synthetase (SepRS) and then con...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00561-17
更新日期:2017-05-09 00:00:00
abstract::Simian virus 40 (SV40) is a nonenveloped DNA virus that traffics through the endoplasmic reticulum (ER) en route to the nucleus, but the mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen to identify cellular genes required for SV40 infection. SV40 infe...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00101-11
更新日期:2011-06-14 00:00:00
abstract:UNLABELLED:The group of proteins known as serine protease autotransporters of Enterobacteriaceae (SPATE) is a growing family of serine proteases secreted to the external milieu by the type V secretion system. Pet toxin and some other SPATE belong to the class 1 cytotoxic SPATE, which have comparable protease strength o...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00838-13
更新日期:2013-12-10 00:00:00
abstract::Pseudomonas aeruginosa, known as one of the leading causes of disease in cystic fibrosis (CF) patients, secretes a variety of proteases. These enzymes contribute significantly to P. aeruginosa pathogenesis and biofilm formation in the chronic colonization of CF patient lungs, as well as playing a role in infections of...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02548-19
更新日期:2019-11-19 00:00:00
abstract:UNLABELLED:Salmonella enterica serovar Typhimurium is one of the most common S. enterica serovars associated with U.S. foodborne outbreaks. S. Typhimurium bacteria isolated from humans exhibit wide-ranging virulence phenotypes in inbred mice, leading to speculation that some strains are more virulent in nature. However...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00154-16
更新日期:2016-03-08 00:00:00
abstract::The clonal population structure of Candida albicans suggests that (para)sexual recombination does not play an important role in the lifestyle of this opportunistic fungal pathogen, an assumption that is strengthened by the fact that most C. albicans strains are heterozygous at the mating type locus (MTL) and therefore...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02740-18
更新日期:2019-02-05 00:00:00
abstract::Maternal infection during pregnancy with a wide range of RNA and DNA viruses is associated with increased risk for schizophrenia and autism in their offspring. A common feature in these exposures is that virus replication induces innate immunity through interaction with Toll-like receptors (TLRs). We employed a mouse ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00176-10
更新日期:2010-10-05 00:00:00
abstract::Regulated organization of the chromosome is essential for faithful propagation of genetic information. In the model bacterium Caulobacter crescentus, the replication terminus of the chromosome is spatially arranged in close proximity to the cytokinetic Z-ring during the cell cycle. Although the Z-ring-associated prote...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02196-20
更新日期:2021-01-26 00:00:00
abstract::Photosynthetic bacteria are capable of producing their own food via photosynthesis. Unsurprisingly, they evolved the ability to move toward better light conditions (i.e., phototaxis). In a recent article in mBio, Chau et al. tuned the wavelength, flux, direction, and timing of light input and characterized the motilit...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.00498-17
更新日期:2017-04-11 00:00:00
abstract::Interferons (IFNs) and autophagy are critical neuronal defenses against viral infection. IFNs alter neuronal autophagy by promoting the accumulation of IFN-dependent LC3-decorated autophagic structures, termed LC3 clusters. Here, we analyzed LC3 clusters in sensory ganglia following herpes simplex virus 1 (HSV-1) infe...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02567-18
更新日期:2019-03-05 00:00:00
abstract::Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of indiv...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02771-18
更新日期:2019-04-16 00:00:00
abstract::Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts. The Anopheles innate immune system is a key regulator of this process, thereby determining vector competence and disease transmission. The role of Anopheles innate immunity factors as agonists...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01631-17
更新日期:2017-10-17 00:00:00
abstract::Cellular sensing of bacterial RNA is increasingly recognized as a determinant of host-pathogen interactions. The intracellular pathogen Listeria monocytogenes induces high levels of type I interferons (alpha/beta interferons [IFN-α/β]) to create a growth-permissive microenvironment during infection. We previously demo...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01223-19
更新日期:2019-10-08 00:00:00
abstract::Microbial photoautotroph-heterotroph interactions underlie marine food webs and shape ecosystem diversity and structure in upper ocean environments. Here, bacterial community composition, lifestyle preference, and genomic- and proteomic-level metabolic characteristics were investigated for an open ocean Synechococcus ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03261-19
更新日期:2020-02-18 00:00:00
abstract:UNLABELLED:Rarely, if ever, has a single bacterial cell been confirmed to simultaneously host two fundamentally different predators. Two such predators are viruses and the predatory prokaryotes known as Bdellovibrio and like organisms. Viruses or bacteriophage are particles requiring prey cells in an active metabolic s...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00051-12
更新日期:2012-04-17 00:00:00
abstract::Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YF...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00819-17
更新日期:2017-08-15 00:00:00
abstract::Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; on...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02654-19
更新日期:2019-12-17 00:00:00
abstract:UNLABELLED:The genus Cyanothece comprises unicellular cyanobacteria that are morphologically diverse and ecologically versatile. Studies over the last decade have established members of this genus to be important components of the marine ecosystem, contributing significantly to the nitrogen and carbon cycle. System-lev...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00214-11
更新日期:2011-10-04 00:00:00