Abstract：
:Retroviral infection involves the reverse transcription of the viral RNA genome into DNA, which is subsequently integrated into the host cell genome. Human immunodeficiency virus type 1 (HIV-1) and other lentiviruses mediate the infection of non-dividing cells through the ability of the capsid protein1 to engage the cellular nuclear import pathways of the target cell and mediate their nuclear translocation through components of the nuclear pore complex2-4. Although recent studies have observed the presence of the capsid protein in the nucleus during infection5-8, reverse transcription and disassembly of the viral core have conventionally been considered to be cytoplasmic events. Here, we use an inducible nuclear pore complex blockade to monitor the kinetics of HIV-1 nuclear import and define the biochemical staging of these steps of infection. Surprisingly, we observe that nuclear import occurs with relatively rapid kinetics (<5 h) and precedes the completion of reverse transcription in target cells, demonstrating that reverse transcription is completed in the nucleus. We also observe that HIV-1 remains susceptible to the capsid-destabilizing compound PF74 following nuclear import, revealing that uncoating is completed in the nucleus. Additionally, we observe that certain capsid mutants are insensitive to a Nup62-mediated nuclear pore complex blockade in cells that potently block infection by wild-type capsid, demonstrating that HIV-1 can use distinct nuclear import pathways during infection. These studies collectively define the spatio-temporal staging of critical steps of HIV-1 infection and provide an experimental system to separate and thereby define the cytoplasmic and nuclear stages of infection by other viruses.
journal_name
Nat Microbioljournal_title
Nature microbiologyauthors
Dharan A,Bachmann N,Talley S,Zwikelmaier V,Campbell EMdoi
10.1038/s41564-020-0735-8subject
Has Abstractpub_date
2020-09-01 00:00:00pages
1088-1095issue
9issn
2058-5276pii
10.1038/s41564-020-0735-8journal_volume
5pub_type
杂志文章abstract：:Competition among microorganisms is a key determinant of successful host colonization and persistence. For Streptococcus pneumoniae, lower than predicted rates of co-colonizing strains suggest a competitive advantage for resident bacteria over newcomers. In light of evolutionary theory, we hypothesized that S. pneumon...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-018-0314-4
更新日期：2019-01-01 00:00:00
abstract：:Leishmania are ancient eukaryotes that have retained the exosome pathway through evolution. Leishmania RNA virus 1 (LRV1)-infected Leishmania species are associated with a particularly aggressive mucocutaneous disease triggered in response to the double-stranded RNA (dsRNA) virus. However, it is unclear how LRV1 is ex...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-018-0352-y
更新日期：2019-04-01 00:00:00
abstract：:Inflammasomes are signalling platforms that are assembled in response to infection or sterile inflammation by cytosolic pattern recognition receptors. The consequent inflammasome-triggered caspase-1 activation is critical for the host defence against pathogens. During infection, NLRP3, which is a pattern recognition r...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-020-00832-5
更新日期：2021-01-11 00:00:00
abstract：:Crimean-Congo haemorrhagic fever (CCHF) is the most medically significant tick-borne disease, being widespread in the Middle East, Asia, Africa and parts of Europe 1 . Increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of CCHF as a public health threat. Ixodid t...
journal_title：Nature microbiology
pub_type： 信件
doi：10.1038/s41564-018-0141-7
更新日期：2018-05-01 00:00:00
abstract：:Here, we developed hCK, a Madin-Darby canine kidney (MDCK) cell line that expresses high levels of human influenza virus receptors and low levels of avian virus receptors. hCK cells supported human A/H3N2 influenza virus isolation and growth much more effectively than conventional MDCK or human virus receptor-overexpr...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-019-0433-6
更新日期：2019-08-01 00:00:00
abstract：: ...
journal_title：Nature microbiology
pub_type： 社论
doi：10.1038/s41564-019-0408-7
更新日期：2019-03-01 00:00:00
abstract：:Helicobacter pylori infection is a proven carcinogen for gastric cancer. Its virulence factor vacuolating cytotoxin A (VacA) promotes more severe disease and gastric colonization. VacA, by an unknown mechanism, usurps lysosomal and autophagy pathways to generate a protected reservoir for H. pylori that confers bacteri...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-019-0441-6
更新日期：2019-08-01 00:00:00
abstract：:As they proliferate, fungi expose antigens at their cell surface that are potent stimulators of the innate immune response, and yet the commensal fungus Candida albicans is able to colonize immuno competent individuals. We show that C. albicans may evade immune detection by presenting a moving immunological target. We...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2016.238
更新日期：2016-12-12 00:00:00
abstract：:Balancing access to antibiotics with the control of antibiotic resistance is a global public health priority. At present, antibiotic stewardship is informed by a 'use it and lose it' principle, in which antibiotic use by the population is linearly related to resistance rates. However, theoretical and mathematical mode...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-019-0410-0
更新日期：2019-07-01 00:00:00
abstract：:The dysregulation of intestinal microbial communities is associated with inflammatory bowel diseases (IBD). Studies aimed at understanding the contribution of the microbiota to inflammatory diseases have primarily focused on bacteria, yet the intestine harbours a viral component dominated by prokaryotic viruses known ...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-018-0210-y
更新日期：2018-09-01 00:00:00
abstract：:Many animal viruses are enveloped in a lipid bilayer taken up from cellular membranes. Because viral surface proteins bind to these membranes to initiate infection, we hypothesized that free virions may also be capable of interacting with the envelopes of other virions extracellularly. Here, we demonstrate this hypoth...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2017.78
更新日期：2017-05-22 00:00:00
abstract：:Despite recent progress, the organization and ecological properties of the intestinal microbial ecosystem remain under-investigated. Here, using a manually curated metabolic module framework for (meta-)genomic data analysis, we studied species-function relationships in gut microbial genomes and microbiomes. Half of gu...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2016.88
更新日期：2016-06-13 00:00:00
abstract：:Influenza A virus is a human pathogen with a genome composed of eight viral RNA segments that replicate in the nucleus. Two viral mRNAs are alternatively spliced. The unspliced M1 mRNA is translated into the matrix M1 protein, while the ion channel M2 protein is generated after alternative splicing. These proteins are...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2016.69
更新日期：2016-05-27 00:00:00
abstract：:Autophagy and interferon (IFN)-mediated innate immunity are critical antiviral defence mechanisms, and recent evidence indicated that tripartite motif (TRIM) proteins are important regulators of both processes. Although the role of TRIM proteins in modulating antiviral cytokine responses has been well established, muc...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-017-0017-2
更新日期：2017-11-01 00:00:00
abstract：:The microbial environment influences animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that during chronic undernutrition, strains of Lactobacillus plantarum, a major commensal partner of Drosophila, promote host juvenile growth...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-017-0038-x
更新日期：2017-12-01 00:00:00
abstract：:The IncC family of broad-host-range plasmids enables the spread of antibiotic resistance genes among human enteric pathogens1-3. Although aspects of IncC plasmid conjugation have been well studied4-9, many roles of conjugation genes have been assigned based solely on sequence similarity. We applied hypersaturated tran...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-020-0775-0
更新日期：2020-11-01 00:00:00
abstract：:CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection1. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases2. While the essential requirements for immune activity are well under...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-020-0691-3
更新日期：2020-05-01 00:00:00
abstract：:Single-cell RNA sequencing has revealed extensive cellular heterogeneity within many organisms, but few methods have been developed for microbial clonal populations. The yeast genome displays unusually dense transcript spacing, with interleaved and overlapping transcription from both strands, resulting in a minuscule ...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-018-0346-9
更新日期：2019-04-01 00:00:00
abstract：:Phylogenetic and geological evidence supports the hypothesis that life on Earth originated in thermal environments and conserved energy through methanogenesis or sulfur reduction. Here we describe two populations of the deeply rooted archaeal phylum Korarchaeota, which were retrieved from the metagenome of a circumneu...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-019-0362-4
更新日期：2019-04-01 00:00:00
abstract：:Glycans are major nutrients for the human gut microbiota (HGM). Arabinogalactan proteins (AGPs) comprise a heterogenous group of plant glycans in which a β1,3-galactan backbone and β1,6-galactan side chains are conserved. Diversity is provided by the variable nature of the sugars that decorate the galactans. The mecha...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-018-0258-8
更新日期：2018-11-01 00:00:00
abstract：:Aichi virus (AiV), an unusual and poorly characterized picornavirus, classified in the genus Kobuvirus, can cause severe gastroenteritis and deaths in children below the age of five years, especially in developing countries1,2. The seroprevalence of AiV is approximately 60% in children under the age of ten years and r...
journal_title：Nature microbiology
pub_type： 信件
doi：10.1038/nmicrobiol.2016.150
更新日期：2016-09-05 00:00:00
abstract：:Dimethylsulfoniopropionate (DMSP) is one of the Earth's most abundant organosulfur molecules, a signalling molecule1, a key nutrient for marine microorganisms2,3 and the major precursor for gaseous dimethyl sulfide (DMS). DMS, another infochemical in signalling pathways4, is important in global sulfur cycling2 and aff...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2017.9
更新日期：2017-02-13 00:00:00
abstract：:Rod-shaped bacteria grow by adding material into their cell wall via the action of two spatially distinct enzymatic systems: the Rod complex moves around the cell circumference, whereas class A penicillin-binding proteins (aPBPs) do not. To understand how the combined action of these two systems defines bacterial dime...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-019-0439-0
更新日期：2019-08-01 00:00:00
abstract：:How does knowing the evolutionary history of microorganisms affect our analysis of microbiological datasets? Depending on the research question, the common ancestry of microorganisms can be a source of confounding variation, or a scaffolding used for inference. For example, when performing regression on traits, common...
journal_title：Nature microbiology
pub_type： 杂志文章,评审
doi：10.1038/s41564-018-0156-0
更新日期：2018-06-01 00:00:00
abstract：:The temporal dynamics of phytoplankton growth and activity have large impacts on fluxes of matter and energy, yet obtaining in situ metabolic measurements of sufficient resolution for even dominant microorganisms remains a considerable challenge. We performed Lagrangian diel sampling with synoptic measurements of popu...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2017.118
更新日期：2017-07-31 00:00:00
abstract：:Understanding metabolism in live microalgae is crucial for efficient biomaterial engineering, but conventional methods fail to evaluate heterogeneous populations of motile microalgae due to the labelling requirements and limited imaging speeds. Here, we demonstrate label-free video-rate metabolite imaging of live Eugl...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2016.124
更新日期：2016-08-01 00:00:00
abstract：:Marine microeukaryotes play a fundamental role in biogeochemical cycling through the transfer of energy to higher trophic levels and vertical carbon transport. Despite their global importance, microeukaryote physiology, nutrient metabolism and contributions to carbon cycling across offshore ecosystems are poorly chara...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-020-00814-7
更新日期：2021-02-01 00:00:00
abstract：:Legionella pneumophila, the causative bacterium for Legionnaires' disease, hijacks host membrane trafficking for the maturation of the Legionella-containing vacuole (LCV). The LCV membrane mainly contains PtdIns4P, which is important for anchoring many secreted Legionella effectors onto the LCV. Here, we identify a cr...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/nmicrobiol.2016.236
更新日期：2016-12-12 00:00:00
abstract：:It is generally believed that exchange of secondary metabolite biosynthetic gene clusters (BGCs) among closely related bacteria is an important driver of BGC evolution and diversification. Applying this idea may help researchers efficiently connect many BGCs to their products and characterize the products' roles in va...
journal_title：Nature microbiology
pub_type： 杂志文章
doi：10.1038/s41564-019-0573-8
更新日期：2019-12-01 00:00:00
abstract：:Cancer arises from the acquisition of multiple genetic and epigenetic changes in host cells over the span of many years, promoting oncogenic traits and carcinogenesis. Most cancers develop following random somatic alterations of key oncogenic genes, which are favoured by a number of risk factors, including lifestyle, ...
journal_title：Nature microbiology
pub_type： 杂志文章,评审
doi：10.1038/nmicrobiol.2017.8
更新日期：2017-02-22 00:00:00
