Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “virus cellular transport”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2026

AP2: an indispensable host factor in virus infection.

Adaptor protein complex 2 (AP2), a central regulator of clathrin-mediated endocytosis and intracellular cargo trafficking, is hijacked by numerous viruses to complete their infectious cycles. This review systematically synthesizes the multifaceted roles of AP2 across the entire viral life cycle, from entry and replication to assembly and release, as well as in immune evasion. By delineating how diverse viruses exploit this key host machinery, we further consolidate the rationale and current progress in developing broad-spectrum antiviral strategies that target AP2 and its regulatory pathways. This work aims to provide a unified perspective on AP2 as a critical host-pathogen interface, offering new insights into viral pathogenesis and antiviral drug discovery.

Humans↗
PubMed1979

Herpes simplex virus type 2 functions expressed during stimulation of human cell DNA synthesis.

Experiments were designed to identify herpes simplex virus type 2 (HSV-2)-specific functions expressed during stimulation of human embryo fibroblast DNA synthesis. Cultures were partially arrested in DNA synthesis by pretreatment with 5-fluorouracil and maintenance in low-serum (0.2%) medium during virus infection. Results showed that continuous [methyl-(3)H]thymidine uptake into cellular DNA was ninefold greater in HSV-2-infected than in mock-infected cultures measured after 24 h of incubation at 42 degrees C. Shifting mock-infected cultures from low- to high-serum (10%) medium also caused some stimulation, but [methyl-(3)H]thymidine uptake was only twofold greater than in cells maintained with low serum. Plating efficiencies of both HSV-2-infected and mock-infected cells at 42 degrees C were essentially the same and ranged from 37 to 76% between zero time and 72 h of incubation. De novo RNA and protein syntheses were continuously required for HSV-2 stimulation of cellular DNA synthesis. HSV-2 infection markedly enhanced transport, phosphorylation, and rate of incorporation of [methyl-(3)H]thymidine into cellular DNA, starting at 3 h and reaching a maximum by 12 h; after 12 h, these processes gradually declined to low levels. In mock-infected cells these processes remained at low levels throughout the observation period. Pretreatment of cells with interferon or addition of arabinofuranosylthymine at the time of virus infection inhibited stimulation caused by HSV-2. 5-Bromodeoxyuridine density-labeled experiments revealed that HSV-2 stimulates predominantly semiconservative DNA replication and some DNA repair. Stimulation of [methyl-(3)H]thymidine into cellular DNA correlated with detection of virus-specific thymidine kinase activity. In conclusion, HSV-2 stimulation of cellular DNA synthesis appeared to involve at least four virus-specific functions: induction of thymidine transport, HSV-2 thymidine kinase activity, semiconservative replication, and repair of cellular DNA.

Arabinonucleotides↗
PubMed1977

Thymidine transport in herpesvirus hominis type 1 and 2 infected BHK 21 cells.

Increase of dThd-uptake 4 to 12 h after infection of BHK or primary rabbit kidney cells with Herpesvirus hominis of type 1 or 2 can be considered as an early function of the virus genome, because the presence of Cyd-Ara does not prevent the increase of uptake. However, increase of uptake can be prevented by addition of actinomycin D and cycloheximide early in the synthetic cycle. Two modes of uptake have been differentiated by kinetic analysis: at low substrate concentration dThd is taken up by 'facilitated transport', whereas at high substrate concentration (above 2-5 micronM) simple diffusion takes place. The Km of transport of normal BHK or primary rabbit kidney cells (1-4 or 0-5 micronM respectively) is not changed after infection. Only the Vmax increases from 8 to 26-6 pmol in BHK cells or from 2-9 to 9-0 pmol in primary rabbit kidney cells. This indicates that 'carrier sites' with identical affinity for dThd-transport are responsible for the increase of transport after infection. This increase of transport is correlated with the induction of a virus coded thymidine kinase (TK) and not with different types of c.p.e. or cellular damage. Transport of BdUrd increases in a similar manner to that of dThd after infection; transport of dCyd or dUrd increases only slightly, whereas the mechanism of dAdo or Urd uptake by infected cells is quite different.

Animals↗
PubMed2025

Influenza A virus RNA localisation and the interceding trafficking pathways of the host cell.

Viruses have evolved to efficiently navigate host cells to deliver, express, and replicate their genetic material. Understanding the mechanisms underlying viral RNA localisation is paramount to designing new antivirals. In this review, we discuss Influenza A Virus (IAV) as a model system to highlight some of the ways in which RNA viruses can hijack the endomembrane systems, as well as nuclear transporters, to achieve the correct localisation of their transcripts. IAV exemplifies a nuclear-replicating RNA virus with a complex and highly regulated RNA localisation and trafficking system within host cells. The virus subverts various vesicular transport systems and nuclear transporters, altering normal cellular functions. IAV RNA trafficking begins during entry; after clathrin-mediated endocytosis, the viral genome (vRNPs) is released into the cytosol after fusion with the endosomal membrane, and it is subsequently imported into the nucleus via the importin system. There, vRNPs engage with most major subnuclear structures and exploit host chromatin, the transcription machinery and splicing apparatus to achieve efficient viral mRNA synthesis and export. Subsequently, newly synthesised vRNPs are rapidly exported from the nucleus and contact the host's recycling endosome network for transport to the plasma membrane. We discuss the critical viral remodelling of the entire endomembrane system, particularly the Rab11 recycling endosome and the endoplasmic reticulum. Lastly, replicated genomes come together into bundles to be inserted in budding virions, and we discuss the current models being proposed and the evidence behind them. Despite advances in understanding these processes, several knowledge gaps remain, particularly regarding the specific export of unspliced IAV transcripts, the remodelling of the endomembrane system, and segment bundling.

Humans↗
PubMed1977

Antiviral action and selectivity of 6-azauridine.

6-Azauridine (AzUrd) is a broad-spectrum antimetabolite that inhibits both DNA and RNA virus multiplication. Prior work indicated that several AzUrd-sensitive viruses induced an increase in the level of uridine kinase, and this might explain the selective activity of AzUrd on such viruses. Present studies compared AzUrd sensitive and resistant viruses with respect to their orotic acid pathways by labeling cells with [14C]-orotic acid during the latent period of viral infection. No differences were detected by this method with either vaccinia, Newcastle disease, or vesicular stomatitis viruses. AzUrd inhibits transport of orotic acid into the cell by 30%, while incorporation of orotic acid into cellular RNA is inhibited by 50% (taking into consideration the 30% already noted) when the highest concentration of antimetabolite is used. This suggests that, in addition to blocking orotidylic acid decarboxylase, AzUrd may act on some other site (sites) of action in the inhibition of virus multiplication.

Antiviral Agents↗
PubMed1975

Analysis of uridine incorporation in chicken embryo cells infected by vesicular stomatitis virus and its temperature-sensitive mutants: uridine transport.

The shut-off of RNA synthesis in chicken embryo cells, after infection with vesicular stomatitis virus, is partially due to a reduced capacity of the infected cells to transport uridine. Permeability to uridine decreases exponentially after infection. This loss of ability to transport uridine may be caused either by structural components of the input virions or may result from the expression of the viral gene products. In the latter case, only minor levels of viral transcription is sufficient to modify cellular permeability, since, even at low multiplicities, RNA minus temperature-sensitive (ts) mutants of vesicular stomatitis virus bring about a significant diminution of uridine incorporation in cells infected under nonpermissive conditions. Experiments with mutants of group III suggest that the M protein of the viral envelope may play a role in the sequence of events that modifies uridine transport. In addition to this cause of the diminution of incorporation of uridine by infected cells, another mechanism is noted which requires protein synthesis.

Animals↗
PubMed2025

Live-cell RNA imaging with the inactivated endonuclease Csy4 enables new insights into plant virus transport through plasmodesmata.

Plant-infecting viruses spread through their hosts by transporting their infectious genomes through intercellular nano-channels called plasmodesmata. This process is mediated by virus-encoded movement proteins. Whilst the sub-cellular localisations of movement proteins have been intensively studied, live-cell RNA imaging systems have so far not been able to detect viral genomes inside the plasmodesmata. Here, we describe a highly sensitive RNA live-cell reporter based on an enzymatically inactive form of the small bacterial endonuclease Csy4, which binds to its cognate stem-loop with picomolar affinity. This system allows imaging of plant viral RNA genomes inside plasmodesmata and shows that potato virus X RNA remains accessible within the channels and is therefore not fully encapsidated during movement. We also combine Csy4-based RNA-imaging with interspecies movement complementation to show that an unrelated movement protein from tobacco mosaic virus can recruit potato virus X replication complexes adjacent to plasmodesmata. Therefore, recruitment of potato virus X replicase is mediated non-specifically, likely by indirect coupling of movement proteins and viral replicase via the viral RNA or co-compartmentalisation, potentially contributing to transport specificity. Lastly, we show that a 'self-tracking' virus can express the Csy4-based reporter during the progress of infection. However, expression of the RNA-binding protein in cis interferes with viral movement by an unidentified mechanism when cognate stem-loops are present in the viral RNA.

Plasmodesmata↗
PubMed1976

Thymidine metabolism and DNA synthesis in Newcastle disease virus-infected cells.

The inhibition of thymidine incorporation into DNA in Newcastle disease virus-infected cells has been studied. At 6 h after infection of L-929 cells at high multiplicity, transport of exogenous thymidine across the cell membrane was inhibited. The kinetics of this inhibition, decreased Vmax with no change in Km, suggest that there are fewer sites available for transport in infected cells. The conversion of thymidine to dTTP was not inhibited. Equilibrium of exogenous thymidine with the acid-soluble pool occurred more slowly and at a lower level of radioactivity than in uninfected cells, and there was a reduction in the rate of incorporation of exogenous thymidine into DNA. The reduction of incorporation into the pool and into DNA was proportionate. The size of total cellular dTTP pools was changed very little in infected cells. DNA synthesized in infected cells in the presence of [3H]BrdUrd had reduced incorporation of tritium but similar buoyant density to that from uninfected cells. The results show that Newcastle disease virus inhibits DNA synthesis directly and, in addition, decreases thymidine transport. Together these account for the overall decrease in thymidine incorporation into DNA of infected cells.

Biological Transport, Active↗
PubMed1978

Lack of correlation between tumorigenicity and level of plasminogen activator in fibroblasts transformed by Rous sarcoma virus.

We have previously isolated, from agar suspension culture, clones of chicken embryo fibroblasts transformed by B77 and Prague strains of Rous sarcoma virus (RSV) that varied in the expression of plasminogen activator activity [Wolf, B. A. & Goldberg, A. (1976) Proc. Natl. Acad. Sci. USA 73, 3613-3617]. All of the clones exhibited an altered cellular morphology, an increased rate of sugar transport, and a high efficiency of colony formation in agar suspension regardless of the level of plasminogen activator. Because B77 and Prague strains of RSV replicate as well as cause sarcomas in chickens, the tumorigenicity of the transformed cells could not be evaluated with clones of these cells. In order to determine the oncogenicity of clones with various levels of plasminogen activator, it was necessary to isolate cells transformed by the replication-defective Bryan strain of RSV, which release noninfectious virus. All of the agar suspension clones of transformed cells, derived by infection of chicken embryo cells with replication-defective Bryan RSV, fell within the continuum observed for B77- and Prague-transformed clones with respect to altered morphology, increased rate of sugar transport, efficiency of colony formation in agar suspension, and variations in plasminogen activator activity. All of the clones, regardless of the level of plasminogen activator, produced tumors when as few as 5 x 10(2) cells were injected into the wing web of 1-day-old chicks. The latency period for tumor formation after injection of cells was similar regardless of the level of plasminogen activator of the injected cell. Primary explants of tumors resulting from inoculation of clones having low, intermediate, or high activator activity displayed a spectrum of activator activity.

Animals↗
PubMed1975

[Electron microscopy studies on the proliferation of foot-and-mouth disease virus in cell cultures. III. Morphogenesis in cytoplasm].

The previous parts have been concerned with the participation of the cell nucleus in the formation of the RNA of FMD virus. However, the actual morphogenesis of the virus takes place in cytoplasm. In BHK cells, changes attributable to virus infection were visible by the second hour, with the formation of threads and large polysome complexes near the nucleus. Viral particles soon appeared between these structures. There were no pronounced foci of viroplasma, and it seemed that they were not necessary. Simultaneously new membranes formed in the cell. Clumps of viral particles were next visible in the cxtoplasma. The clumps became enveloped and were transported in this way to the periphery of the cell. Elsewhere there was uptake of particles in autophagic vacuoles, an expression of cellular defensive processes. In ultra-thin sections the virions measured 21-25 nm. Within vacuoles the inner part of the virus, the nucleoid, showed greater contrast than the periphery, the capsid. At first there were only slight changes in mitochondria. Liberation of virus by cell rupture occurred only after severe damage to the cell, particularly the lysosome membranes.

Animals↗
PubMed1979

Change of isozyme pattern during activation of a transforming gene product: its relation to other biochemical markers of cellular transformation and differentiation.

Isozyme patterns of leucine aminotransferase were studied in connection with glucose transport and DNA synthesis during the activation and deactivation of the transforming gene product in rat kidney cells transformed by one Rous sarcoma virus mutant (which has a temperature-sensitive lesion in its transforming gene. On temperature shift-down of confluent transformed cells grown at 40 degrees C in the presence of fresh serum, isozyme III of leucine aminotransferase appeared in 12--20 h, with increasing amounts from 24 to 48 h. Upon temperature shift-up, isozyme I became the predominant form in these cells within 4 days, the major change occurring within the first 24 h. The rate of protein turnover was similar to the rate of loss of isozymes I and III during temperature shift-down and shift-up, respectively. A stimulation of incorporation of [3H]thymidine into DNA was observed within 8--12 h after temperature shift-down of the transformed cells. For the maintenance of stimulated DNA synthesis for at least 16 h, continued exposure to the permissive temperature is not necessary. Stimulation of glucose transport occurred prior to the stimulation of [3H]thymidine incorporation. The isozymes of leucine aminotransferase also changed during the in vitro differentiation of Yaffee L6A cells in such a way that isozyme I represented the major part of this enzyme in the fused myotube, and isozyme III was more predominant in the less differentiated state (mononucleated cells).

Animals↗
PubMedDate not supplied

[Cell proliferation induction in a monolayer chick embryo culture by the Sendai virus].

The response of cells on monolayer chick embryo cultures to infection with Sendai virus was studied. Total infection leads to the death of the cells within 3--5 days postinoculation which permits this system to be considered as lytic. Its significant difference from other systems with the lytic outcome of interaction of non-oncogenic viruses with animal cells consists in marked enhancement of production of proper cellular RNA and proteins in the infected cells and an increase in their division rate preceeding their death.

Animals↗
PubMed1977

Cell killing by simian virus 40: impairment of membrane formation and function.

Simian virus 40 infection of the CV-1 line of green monkey kidney cells results in the release of mitochondrial malic dehydrogenase as early as 24 h. Released malic dehydrogenase is detected in the cytoplasm prior to its appearance in the overlay medium. Infected cells lose the ability to consume oxygen between 48 and 56 h, and damage to the elctron transport system is indicated. Nevertheless, cellular ATP levels remain high as late as 72 h. Infection leads to a stimulation of membrane phospholipid synthesis, which reaches a peak at about 32 h. This is followed by a severe decline in new membrane synthesis, which correlates in time with the release of cytoplasmic lactic dehydrogenase into the overlay media. Lactic dehydrogenase release precedes the accumulation of trypan blue-stainable cells by about 6 h. Infection had no effect on the turnover of prelabeled membrane phospholipids. An early simian virus 40 mutant, tsA58, and a late mutant, tsB11, are both less effective than wild-type virus at causing reduced levels of phospholipid synthesis, enzyme release, and the accumulation of trypan blue-stainable cells. Another late mutant, tsB8, is similar to wild-type virus in these respects. At 64 h, there is no detectable cell-associated lactic dehydrogenase and nearly all the cells are trypan blue stainable. Nevertheless, at concentrations of deoxyglucose in the medium below the transport Km, deoxyglucose uptake was similar in infected and control cultures. With higher concentrations of deoxyglucose in the medium, uptake by the infected cultures exceeded that by the control cultures.

Adenosine Triphosphate↗
PubMed2025

Fluorescence Loss After Photoactivation (FLAPh): A Pulse-Chase Cellular Assay for Understanding Kinetics and Dynamics of Viral Inclusions.

Influenza A virus (IAV) relies on host cellular machinery for replication. Upon infection, the eight genomic segments, independently packed as viral ribonucleoproteins (vRNPs), are released into the cytosol before nuclear import for viral replication. After nucleocytoplasmic transport, the resulting progeny vRNPs reach the cytosol, accumulating in highly mobile and dynamic viral inclusions that display liquid properties. Being sites postulated to support IAV genome assembly, the biophysical properties of IAV inclusions may be critical for function. In agreement, imposing liquid-to-solid transitions was demonstrated to impact viral replication negatively. Therefore, screening for host factors or compounds able to alter the material properties may provide the molecular basis for how influenza genomic complex forms as well as identify novel antivirals. Conventional techniques employed to investigate biomolecular condensates' material properties include fluorescence correlation spectroscopy, raster image correlation spectroscopy, single molecule or microrheology particle tracking, and Fluorescence Recovery After Photobleaching (FRAP). These approaches allow measuring molecular dynamics in systems that do not move very much. However, the analysis of highly mobile intracellular condensates, such as IAV inclusions, poses significant challenges as these structures not only constantly move within the cell but also exchange material, fusing, and dividing, rendering the quantitation of internal rearrangements and diffusion coefficients of molecules within condensates inaccurate. As an alternative, we opted for measuring the kinetics and the exchange of material between IAV inclusions using the Fluorescence Loss After Photoactivation (FLAPh) technique. It involves pulse photoactivation of individual or pools of viral inclusions in the cell, and chasing over time in photoactivated and non-photoactivated regions. This approach is suitable for quantifying the movement and spatial distribution of components within inclusions over time, enabling the determination of both the distance and speed from a specific cellular location. As a result, this method allows the quantification of decay profiles, half-lives, decay constant rate, and mobile and immobile fractions in viral inclusions. It, therefore, enables high throughput screenings for compounds or host factors that affect this dynamism and indirectly allows assessing the material properties of IAV inclusions.

Humans↗
PubMed1976

Sodium-stimulated alpha-aminoisobutyric acid transport by membrane vesicles from simian virus-transformed mouse cells.

Uptake of alpha-aminoisobutyric acid, by membrane vesicles derived principally from the plasma membrane and endoplasmic reticulum of mouse 3T3 cells transformed by simian virus 40, is stimulated by sodium chloride. Both in the presence and absence of Na+ uptake is time-dependent and osmotically sensitive. The Na+-stimulated uptake is inhibited by other amino acids. The kinetics of transport of alpha-aminoisobutyric acid are shown to be biphasic both in whole cells and in the membrane vesicles. Only the high affinity system is stimulated by sodium in the membrane vesicles. These results demonstrate that observations made on living cells correlate with observations made on isolated membrane vesicles, and indicate that these membrane vesicles have retained the cellular amino acid transport system functionally intact.

Amino Acids↗
PubMed1979

Modulation of glucose uptake in animal cells. Studies using plasma membrane vesicles isolated from nontransformed and simian virus 40-transformed mouse fibroblast cultures.

Plasma membrane vesicles isolated from nontransformed and Simian virus 40-transformed mouse fibroblast cultures catalyzed carrier-mediated D-glucose transport without detectable metabolic conversion to glucose 6-phosphate. Glucose transport activity was stereospecific, temperature-dependent, sensitive to inactivation by p-chloromercuriphenylsulfonate, and accompanied plasma membrane material during subcellular fractionation. D-Glucose efflux from vesicles was inhibited by phloretin, an inhibitor of glucose uptake in intact cells. Cytochalasin B, a potent inhibitor of glucose uptake when tested with the intact cells used for vesicle isolation did not inhibit glucose transport in vesicles despite the presence of high affinity cytochalasin binding sites in isolated membranes. The enhanced glucose uptake observed in intact cells after viral transformation was not expressed in vesicles: no significant differences in glucose transport specific activity could be detected in vesicle preparations from nontransformed and transformed mouse fibroblast cultures. These findings indicate that cellular components distinct from glucose carriers can mediate changes in glucose uptake in mouse fibroblast cultures in at least two cases: sensitivity to inhibition by cytochalasin B and the enhanced cellular sugar uptake observed after viral transformation.

Animals↗
PubMed1976

Regulation of active alpha-aminoisobutyric acid transport expressed in membrane vesicles from mouse fibroblasts.

Membrane vesicles isolated from untransformed Balb/c and Swiss mouse fibroblasts and from those transformed by simian virus 40 catalyzed carrier-mediated uptake of L-alpha-aminoisobutyric acid. Concentrative uptake required the presence of a Na+ gradient (external Na+ greater than internal Na+) and occurred independently of endogenous (Na+ + K+) ATPase activity. This process is electrogenic, since uptake was stimulated by a K+ diffusion gradient (internal greater external) in the presence of valinomycin or by the addition of the Na+ salt of a permeant ion, conditions expected to create an interior-negative membrane potential. Both the initial rate of concentrative uptake of L-alpha-aminoisobutyric acid and its maximal accumulation, driven by a standard Na+ gradient, were decreased in vesicles from density-inhibited, untransformed cells and increased in those from cells transformed by simian virus 40 compared with vesicles from proliferating untransformed cells. An increased maximal velocity (Vmax) of uptake stimulated by Na+ gradient was observed in vesicles from transformed cells compared with those from untransformed cells, suggesting an increase in the number of carriers or in their mobility. Since the relative extent of accumulation of this model amino acid driven by a standard Na+ gradient also differed with growth or transformed status, an additional possibility for cellular regulation of this process could be alteration of membrane Na+ permeability or carrier response to Na+.

Adenosine Triphosphatases↗
PubMed1977

Dipyridamole, an inhibitor of mengovirus replication in FL and L cells.

Dipyridamole showed an antiviral activity aganinst mengovirus in FL cells using the agar diffusion plaque inhibition test, plaque reduction test, tube titration test, and virus yield test after one replication cycle. With the last two tests mentioned above the inhibitory action was also confirmed in L cells. In consequence of the known transport inhibition of uridine into the cell in presence of dipyridamole only a very small incorporation of 3H-uridine into acid-insoluble material could be demonstrated. Applying the method of prelabelling of FL cells at 16 degrees C for 1 h with subsequent addition of dipyridamole the drug failed to show an effect on cellular RNA synthesis per se in uninfected cells whereas the viral RNA synthesis in mengo-virus-infected L cells was completely depressed.

Antiviral Agents↗