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an internal ribosome entry site promotes translation of a novel siv pr55(gag) isoform.in complex retroviruses including simian immunodeficiency virus (siv) and human immunodeficiency virus type 1 (hiv-1), the major structural proteins are encoded by the gag gene and translated as a precursor polyprotein, pr55(gag). an internal ribosome entry site (ires) within the coding region of hiv-1 and hiv type 2 (hiv-2) gag rna mediates expression of n-terminally truncated isoforms of the precursor polyprotein. in this study, we identify an n-terminally truncated siv pr55(gag) isoform expre ...200616494914
recruitment of the adaptor protein 2 complex by the human immunodeficiency virus type 2 envelope protein is necessary for high levels of virus release.the envelope (env) protein of human immunodeficiency virus type 2 (hiv-2) and the hiv-1 vpu protein stimulate the release of retroviral particles from human cells that restrict virus production, an activity that we call the enhancement of virus release (evr). we have previously shown that two separate domains in the hiv-2 envelope protein are required for this activity: a glycine-tyrosine-x-x-hydrophobic (gyxxtheta) motif in the cytoplasmic tail and an unmapped region in the ectodomain of the pr ...200616501101
the effect of a methyl or 2-fluoroethyl substituent at the n-3 position of thymidine, 3'-fluoro-3'-deoxythymidine and 1-beta-d-arabinosylthymine on their antiviral and cytostatic activity in cell culture.thymidine (thd), 1-beta-d-arabinosylthymine (ara-t) and 3'-fluoro-3'-deoxythymidine (flt) have been substituted at n-3 by a methyl or a 2-fluoroethyl group. flt and ara-t are markedly inhibitory against human immunodeficiency virus type 1 (hiv-1) and hiv-2, and herpes simplex virus type 1 (hsv-1) and hsv-2, respectively. modification at n-3 of these compounds markedly decreases both the antiviral and cytostatic activity of the parent compounds flt and ara-t except for n-3-(methyl)-thd that prove ...200616542002
development and evaluation of a real-time rt-pcr assay for quantification of cell-free human immunodeficiency virus type 2 using a brome mosaic virus internal control.quantification of cell-free virus in plasma is important for monitoring disease progression and for assessing the response to antiretroviral therapy in both human immunodeficiency type 1 and type 2 (hiv-1, hiv-2) infections. although commercial assays suitable for hiv-1 quantification have been used for more than a decade, no commercial assays are yet available for the measurement of cell-free hiv-2. we have therefore developed a novel real-time rt-pcr assay which, unlike previously described 'i ...200616563526
worldwide molecular epidemiology of hiv.human immunodeficiency virus (hiv) is the worldwide disseminated causative agent of acquired immunodeficiency syndrome (aids). hiv is a member of the lentivirus genus of retroviridae family and is grouped in two types named hiv-1 and hiv-2. these viruses have a notable ability to mutate and adapt to the new conditions of human environment. a large incidence of errors at the transcriptional level results in changes on the genetic bases during the reproductive cycle. the elevated genomic variabili ...200616583048
hiv protease cleaves poly(a)-binding protein.the pabp [poly(a)-binding protein] is able to interact with the 3' poly(a) tail of eukaryotic mrna, promoting its translation. cleavage of pabp by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis. we report that infection of mt-2 cells with hiv-1 leads to efficient proteolysis of pabp. analysis of pabp integrity was carried out in bhk-21 (baby-hamster kidney) and cos-7 cells upon individual expression of the protease ...200616594896
molecular investigation of human immunodeficiency virus type 2 subtype a cases in south korea.we investigated the molecular characteristics of human immunodeficiency virus type 2 (hiv-2) subtype a isolates to clarify the transmission mode of hiv-2 within korea. these findings indicated that the viruses from the six patients infected within korea formed a distinct subcluster in the phylogenetic tree and might have been transmitted from one source.200616597889
no association between gb virus c infection and disease progression in hiv-2-infected patients from the french anrs hiv-2 cohort.out of 183 hiv-2-infected patients tested in the anrs co8 hiv-2 cohort, 69 were exposed to gb virus c (gbv-c), yielding a prevalence of 38% (95% ci 30.7, 45.2). there was no significant difference between the cd4 cell count and hiv-2-rna plasma viral load in patients exposed and not exposed to gbv-c. after adjusting for age and cd4 cell count, co-infection with gbv-c was not associated with clinical progression (hazard ratio 0.78; 95% ci 0.24-2.56, 16 clinical events).200616603866
using hidden markov models and observed evolution to annotate viral genomes.motivation: ssrna (single stranded) viral genomes are generally constrained in length and utilize overlapping reading frames to maximally exploit the coding potential within the genome length restrictions. this overlapping coding phenomenon leads to complex evolutionary constraints operating on the genome. in regions which code for more than one protein, silent mutations in one reading frame generally have a protein coding effect in another. to maximize coding flexibility in all reading frames, ...200616613911
tipranavir: pnu 140690, tipranivir.tipranavir [pnu 140690, tipranivir, aptivus] is a second-generation hiv dihydropyrone (a sulphonamide derivative), nonpeptidic protease inhibitor (nppi) discovered by pharmacia & upjohn (now pfizer) in the us. the compound is in development with boehringer ingelheim. tipranavir has potent in vitro activity against a variety of hiv-1 laboratory strains and clinical isolates, including those resistant to ritonavir, as well as hiv-2. tipranavir has been shown to act synergistically with other antir ...200616620137
human immunodeficiency virus serotyping on dried serum spots as a screening tool for the surveillance of the aids epidemic.many studies have demonstrated the utility of the dried blood spot (dbs) or dried plasma/serum spot (dss) method for serological and molecular diagnosis of hiv infection. here, we report on the description of a serotyping assay performed on dss, and its application to a national surveillance program of hiv variants. we combined serotyping assays that we developed previously to discriminate between hiv-1 and hiv-2, between hiv-1 group o and hiv-1 group m, and between b and non-b subtypes of hiv-1 ...200616622871
theta-defensins prevent hiv-1 env-mediated fusion by binding gp41 and blocking 6-helix bundle formation.retrocyclin-1, a -defensin, protects target cells from human immunodeficiency virus, type 1 (hiv-1) by preventing viral entry. to delineate its mechanism, we conducted fusion assays between susceptible target cells and effector cells that expressed hiv-1 env. retrocyclin-1 (4 microm) completely blocked fusion mediated by hiv-1 envs that used cxcr4 or ccr5 but had little effect on cell fusion mediated by hiv-2 and simian immunodeficiency virus envs. retrocyclin-1 inhibited hiv-1 env-mediated fusi ...200616648135
hiv type 2 demyelinating encephalomyelitis.a human immunodeficiency virus (hiv) type 2 (hiv-2)-infected african patient developed inflammatory demyelinating lesions of the optic nerves, spinal cord, and brain, which coincided with a decreasing cd4 cell count and with active hiv-2 replication. this case provides evidence that hiv-2 is neurotropic, extends the range of known hiv-2-associated neurological complications, and confirms the overlap between the neurological complications of hiv type 1 and hiv-2 infection.200616652302
sensitivity of the multispot hiv-1/hiv-2 rapid test using samples from human immunodeficiency virus type 1-positive individuals with various levels of exposure to highly active antiretroviral therapy.the multispot hiv-1/hiv-2 rapid test detects human immunodeficiency virus type 1 (hiv-1) gp41 antibodies, which can wane over time in some hiv-1-infected populations, resulting in false-negative screening results. multispot sensitivity was 100% using 248 sera from one such population, and it correctly identified serostatus in individuals who previously tested false negative with rapid testing.200616672414
use of an acute seroconversion panel to evaluate a third-generation enzyme-linked immunoassay for detection of human immunodeficiency virus-specific antibodies relative to multiple other assays.a human immunodeficiency virus type 1 (hiv-1)/hiv-2 antibody screening assay, the genetic systems hiv-1/hiv-2 plus o eia, was compared to several established screening or confirmatory tests using an acute hiv seroconversion panel. the hiv-1/hiv-2 plus o eia showed an improved sensitivity over all tested antibody screening methods, and detected antibody in 7 of 19 specimens found to be negative by a first-generation eia but positive for the presence of hiv rna.200616672422
(a3) hiv phenotypes, oral lesions, and management of hiv-related disease.workshop participants discussed: the role of hiv subtypes in disease; the treatment of oral candidiasis; the relationship between and among viral load, cd4+ counts, oral candidiasis and oral hairy leukoplakia, pigmentation; and the development of a reliable oral index to predict disease progression. regarding hiv, the literature revealed that type i (hiv-i), in particular group m, is involved in the majority (90%) of documented infections, and groups n and o to a lesser extent. viral envelope di ...200616672562
cleavage, a real turn-off? hiv-mediated proteolysis of pabp1.in this issue of the biochemical journal, alvarez and colleagues have identified pabp1 [poly(a)-binding protein 1] as a target of protease cleavage during hiv infection. the study shows that hiv-1, hiv-2 and mouse mammary tumour virus, but not other retroviruses, target pabp1 for cleavage and identifies cleavage sites within the rna-recognition motifs and c-terminal region of the protein. this suggests that pabp1 cleavage may be important in the shut-off of host translation during hiv infection. ...200616703665
prevalence of human immunodeficiency virus infection among tuberculosis suspect patients in accra, ghana.acquired immunodeficiency syndrome is a major public health concern worldwide, particularly in ghana, where recent reports indicate an increase of the disease. a close association between infection with human immunodeficiency virus (hiv) and tuberculosis (tb) is well known. a previous study showed a 16.8% seroprevalence of hiv in tb patients on admission at the chest clinic of the korle-bu teaching hospital. however this was in severely ill patients on admission and there was a likely selection ...200616722357
evolution of hiv/aids prevention programs--united states, 1981-2006.when the first cases of what would become known as acquired immunodeficiency syndrome (aids) were reported in 1981, the magnitude of the epidemic and the numbers of deaths were unimaginable. during the next 25 years, an unprecedented mobilization of individual, community, and government resources was directed at stopping the epidemic. cdc currently supports a wide range of human immunodeficiency virus (hiv) prevention activities in the united states, including 1) collection of behavioral and hiv ...200616741496
no association between seropositivity for hepatitis c virus and lichen planus: a case control study.the epidemiological association of lichen planus (lp) with hepatitis c virus (hcv) infection has been recorded from some countries and hcv rna3 has been isolated from lesional skin in patients with lp and chronic hcv infection. the observed geographical differences regarding hcv infection and lp could be immuno-genetically related.200616766832
multicenter evaluation of the bayer advia centaur hiv 1/o/2 enhanced (ehiv) assay.it is important that serological assays detect antibodies to human immunodeficiency virus (hiv) in all infected individuals, including those infected with less prevalent, more diverse subtypes.200616769045
role of invariant thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity.sequence variability associated with human immunodeficiency virus type 1 (hiv-1) is useful for inferring structural and/or functional constraints at specific residues within the viral protease. positions that are invariant even in the presence of drug selection define critically important residues for protease function. while the importance of conserved active-site residues is easily understood, the role of other invariant residues is not. this work focuses on invariant thr80 at the apex of the ...200616809296
in vitro replication capacity of hiv-2 variants from long-term aviremic individuals.to establish whether efficient suppression of virus replication in hiv-2-infected individuals is associated with low replicative capacity of hiv-2, replication kinetics of hiv-2 variants from long-term aviremic individuals was analyzed and compared with that of the relatively slow-replicating hiv-1 variants from asymptomatics and long-term nonprogressors (as/ltnp). on average, hiv-2 from aviremic individuals had lower replication rates than hiv-1 variants from as/ltnp in cells of 8 donors (0.45 ...200616814357
genomic sites of human immunodeficiency virus type 2 (hiv-2) integration: similarities to hiv-1 in vitro and possible differences in vivo.retroviruses have distinct preferences in integration site selection in the host cell genome during in vitro infection, with human immunodeficiency virus type 1 (hiv-1) integration strongly favoring transcriptional units. additionally, studies with hiv-1 have shown that the genomic site of proviral integration may impact viral replication, with integration in heterochromatin associated with a block in viral transcription. hiv-2 is less pathogenic than hiv-1 and is believed to have a lower replic ...200616840312
isolation of an active lv1 gene from cattle indicates that tripartite motif protein-mediated innate immunity to retroviral infection is widespread among mammals.lv1/trim5alpha (tripartite motif 5alpha) has recently emerged as an important factor influencing species-specific permissivity to retroviral infection in a range of primates, including humans. old world monkey trim5alpha blocks human immunodeficiency virus type 1 (hiv-1) infectivity, and the human and new world monkey trim5alpha proteins are inactive against hiv-1 but active against divergent murine (n-tropic murine leukemia virus [mlv-n]) and simian (simian immunodeficiency virus from rhesus ma ...200616840314
peptides derived from hiv-1, hiv-2, ebola virus, sars coronavirus and coronavirus 229e exhibit high affinity binding to the formyl peptide receptor.peptides derived from the membrane proximal region of fusion proteins of human immunodeficiency viruses 1 and 2, coronavirus 229 e, severe acute respiratory syndrome coronavirus and ebola virus were all potent antagonists of the formyl peptide receptor expressed in chinese hamster ovary cells. binding of viral peptides was affected by the naturally occurring polymorphisms at residues 190 and 192, which are located at second extracellular loop-transmembrane helix 5 interface. substitution of r190 ...200616842982
tar-rna recognition by a novel cyclic aminoglycoside analogue.the formation of the tat-protein/tar-rna complex is a crucial step in the regulation of human immunodeficiency virus (hiv)-gene expression. to obtain full-length viral transcripts the tat/tar complex has to recruit the positive transcription elongation factor complex (p-eftb), which interacts with tar through its cyclin t1 (cyct1) component. mutational studies identified the tar hexanucleotide loop as a crucial region for contacting cyct1. interfering with the interaction between the tat/cyct1 c ...200616855296
coassembly and complementation of gag proteins from hiv-1 and hiv-2, two distinct human pathogens.approximately one million people in the world are dually infected with both hiv-1 and hiv-2. to identify potential interactions between these two human pathogens, we examined whether hiv-1 and hiv-2 gag proteins can coassemble and functionally complement each other. we generated hiv-1- and hiv-2-based vectors with mutations in gag; compared with wild-type vectors, these mutants had drastically decreased viral titers. coexpression of the mutant hiv-1 and hiv-2 gag could generate infectious viruse ...200616857594
contribution of vpu, env, and nef to cd4 down-modulation and resistance of human immunodeficiency virus type 1-infected t cells to superinfection.human immunodeficiency virus type 1 (hiv-1) utilizes vpu, env, and nef to down-modulate its primary cd4 receptor from the cell surface, and this function seems to be critical for the pathogenesis of aids. the physiological relevance of cd4 down-modulation, however, is currently not well understood. in the present study, we analyzed the kinetics of cd4 down-modulation and the susceptibility of hiv-1-infected t cells to superinfection using proviral hiv-1 constructs containing individual and combi ...200616873261
indeterminate human immunodeficiency virus western blot results in iranian patients with discordant screening assay results.the western blot (wb) assay is the most widely accepted confirmatory assay for the detection and confirmation of antibodies to human immunodeficiency virus type 1 (hiv-1) and 2 (hiv-2). however, indeterminate wb reactivity to hiv-1 and hiv-2 proteins may occur in individuals who do not appear to be infected with hiv.200616883439
characterization of the human chemerin receptor--chemr23/cmklr1--as co-receptor for human and simian immunodeficiency virus infection, and identification of virus-binding receptor domains.studies were conducted to elucidate co-receptor spectrum and function of the inflammatory receptor, cmklr1/chemr23, which was recently identified as the receptor for the cystatin-like chemoattractant, tig2, also named chemerin. an infection model was applied based on stably transfected np-2.cd4 host cells expressing various co-receptor constructs and exposed to panels of hiv-1, hiv-2 and siv primary isolates. in a panel of 27 hiv-1 isolates tested, 12 isolates could use cmklr1/chemr23. as expect ...200616904155
performance evaluation of three automated human immunodeficiency virus antigen-antibody combination immunoassays.three fourth-generation antigen/antibody combination assays (elecsys, axsym, architect hiv) and two third-generation (axsym, centaur) hiv antibody immunoassays were evaluated. the evaluation panel of 479 samples included: nine tissue culture derived hiv-1 strains at four different p24 antigen concentrations (n=36), a p24 antigen sensitivity panel (n=10), 149 hiv-1 or hiv-2 confirmed antibody positive samples, ten anti-hiv-1 positive low titer samples, three seroconversion panels (n=21), and 253 ...200616313975
conserved amino acids of the human immunodeficiency virus type 2 vpx nuclear localization signal are critical for nuclear targeting of the viral preintegration complex in non-dividing cells.the hiv-2 viral accessory protein vpx is related to, but distinct from the vpr protein of hiv-1. vpx is packaged into virions and as a component of the viral preintegration complex (pic) is required for efficient virus replication in non-dividing cells. we have previously reported that the minimal transferable region of vpx that contained karyophilic properties was aa 65 to 72. analysis of vpx sequences from various hiv-2/siv strains reveals that this region contains highly conserved amino acids ...200616325220
mutations in the u5 sequences adjacent to the primer binding site do not affect trna cleavage by rous sarcoma virus rnase h but do cause aberrant integrations in vivo.in most retroviruses, the first nucleotide added to the trna primer becomes the right end of the u5 region in the right long terminal repeat (ltr); the removal of this trna primer by rnase h defines the right end of the linear double-stranded dna. most retroviruses have two nucleotides between the 5' end of the primer binding site (pbs) and the ca dinucleotide that will become the end of the integrated provirus. however, human immunodeficiency virus type 1 (hiv-1) has only one nucleotide at this ...200616352569
simian immunodeficiency virus vpx is imported into the nucleus via importin alpha-dependent and -independent pathways.vpx protein of human immunodeficiency virus type 2/simian immunodeficiency virus (siv) has been implicated in the transport of the viral genome into the nuclei of nondividing cells. the mechanism by which vpx enters the nucleus remains unknown. here we have identified two distinct noncanonical nuclear localization signals (nlss) in vpx of siv(smpbj1.9) and defined the pathways for its nuclear import. although nuclear targeting signals identified here are distinct from known nuclear import signal ...200616352576
comparative study on the structure and cytopathogenic activity of hiv vpr/vpx proteins.the three-dimensional (3-d) structure of human immunodeficiency virus type 2 (hiv-2) vpr/vpx was predicted by homology modeling based on the nmr structure of human immunodeficiency virus type 1 (hiv-1) vpr. the three proteins similarly have three major amphipathic alpha-helices. in contrast to hiv-1 vpr, vpr/vpx of hiv-2 have a long n-terminal loop and clustered prolines in the second half of the c-terminal loop. hiv-2 vpx uniquely contains a long region between the second and third major helice ...200616153874
structure of the zinc finger domain encompassing residues 13-51 of the nucleocapsid protein from simian immunodeficiency virus.the ncps (nucleocapsid proteins) of hiv-1 (hiv type 1), hiv-2 and siv (simian immunodeficiency virus) are small highly basic proteins, characterized by the presence of two cchc zf (zinc finger) domains. ncps, closely associated with the dimeric rna genome in the core of the virus particle, were shown to promote the specific encapsidation of the viral rna and are implicated in reverse transcription. solution structure of the hiv-1 ncp7 and complexes of ncp7 with rna or dna showed the critical rel ...200616229684
the absence of anti-tat antibodies is associated with risk of disease progression in hiv-2 infection.the tat protein of human immunodeficiency virus (hiv) is essential for viral replication and has extracellular pathogenic activity. we sought to determine whether the anti-tat antibody response was predictive of disease progression in 144 hiv type 2 (hiv-2)-infected subjects observed longitudinally between 1985 and 2003. sixty-eight percent of the subjects tested positive for anti-tat antibodies, with reactivity notably established early after seroconversion and stably maintained over the course ...200616941341
non-nucleoside hiv-1 reverse transcriptase inhibitors, part 7. synthesis, antiviral activity, and 3d-qsar investigations of novel 6-(1-naphthoyl) hept analogues.a series of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (hept) analogues bearing a 6-(1-naphthoyl) group of non-nucleoside human immunodeficiency virus (hiv) reverse transcriptase inhibitors were synthesized and evaluated for their activity against hiv-1 and hiv-2. it was found that most of these compounds showed good activity against hiv-1. among them, compound 5-isopropyl-6-(1-naphthoyl)-1-[(2e)-3-phenylallyl]-2,4-pyrimidinedione (23) displayed the greatest inhibitory potency (ic(5 ...200616946529
morphological study on biologically distinct vpx/vpr mutants of hiv-2.we have previously shown that human immunodeficiency virus type 2 (hiv-2) without functional vpx and vpr genes is severely defective for viral growth in lymphocytic cells, and suggested that the virions produced in the absence of vpx and vpr are critically damaged. to examine the nature of replication-defect for the vpx/vpr double mutant, we quantitatively and morphologically studied the virions produced in cells transfected or infected with wild type clone, single (vpx and vpr mutants) or the d ...200616953064
high frequency of genetic recombination is a common feature of primate lentivirus replication.recent studies indicate that human immunodeficiency virus type 1 (hiv-1) recombines at exceedingly high rates, approximately 1 order of magnitude more frequently than simple gammaretroviruses such as murine leukemia virus and spleen necrosis virus. we hypothesize that this high frequency of genetic recombination is a common feature of primate lentiviruses. alternatively, it is possible that hiv-1 is unique among primate lentiviruses in possessing high recombination rates. among other primate len ...200616973569
nuclear export of simian immunodeficiency virus vpx protein.lentiviruses, human immunodeficiency viruses (hivs), and simian immunodeficiency viruses (sivs) are distinguished from oncoretroviruses by their ability to infect nondividing cells such as macrophages. retroviruses must gain access to the host cell nucleus for replication and propagation. hiv and siv preintegration complexes (pic) enter nuclei after traversing the central aqueous channel of the limiting nuclear pore complex without membrane breakdown. among the nucleophilic proteins, namely, mat ...200616987982
proviral progeny of heterodimeric virions reveal a high crossover rate for human immunodeficiency virus type 2.human immunodeficiency virus type 1 (hiv-1), the causative agent of aids in humans, exhibits a very high rate of recombination. bearing in mind the significant epidemiological and clinical contrast between hiv-2 and hiv-1 as well as the critical role that recombination plays in viral evolution, we examined the nature of hiv-2 recombination. towards this end, a strategy was devised to measure the rate of crossover of hiv-2 by evaluating recombinant progeny produced exclusively by heterodimeric vi ...200617020945
increased frequency of circulating ccr5+ cd4+ t cells in human immunodeficiency virus type 2 infection.ccr5 expression determines susceptibility to infection, cell tropism, and the rate of human immunodeficiency virus type 1 (hiv-1) disease progression. ccr5 is also considered the major hiv-2 coreceptor in vivo, in spite of broad coreceptor use in vitro. here we report a significantly increased proportion of memory-effector cd4 t cells expressing ccr5 in hiv-2-infected patients correlating with cd4 depletion. moreover, hiv-2 proviral dna was essentially restricted to memory-effector cd4, suggesti ...200617035326
multicenter evaluation of a new 4th generation hiv screening assay elecsys hiv combi.fourth-generation screening assays which permit a simultaneous detection of human immunodeficiency virus (hiv) antigen and antibody reduce the diagnostic window on average by four days in comparison to third-generation antibody assays. recently, the new automated elecsys hiv combi was compared in a multicenter study to alternative fourth- and third-generation assays, p24 antigen test and hiv-1 rna rt-pcr. a total of 104 serocon-version panels, samples of the acute phase of infection after seroco ...200617078473
human trim5alpha mediated restriction of different hiv-1 subtypes and lv2 sensitive and insensitive hiv-2 variants.in order to characterize the antiviral activity of human trim5alpha in more detail human derived indicator cell lines over expressing wild type human trim5alpha were generated and challenged with hiv-1 and hiv-2 viruses pseudotyped with hiv envelope proteins in comparison to vsv-g pseudotyped particles. hiv envelope protein pseudotyped particles (hiv-1[nl4.3], hiv-1[bal]) showed a similar restriction to infection (12 fold inhibition) compared to vsv-g pseudotyped viruses after challenging tzm-hu ...200617087820
[primary human immunodeficiency virus infection revealed by psychiatric symptoms].any atypical psychiatric disorder, especially if associated with somatic manifestations and when any psychiatric antecedents are missing, should lead to search for an organic pathology, and notably a human immunodeficiency virus (hiv) infection. in the case of primary human immunodeficiency virus infection (phi), which is often symptomatic, the diagnosis is seldom made, probably because of atypical or non specific manifestations. therefore, it is essential to consider such a diagnosis, because i ...200617099559
an adaptation of recombinant vaccinia-based elispot and intracellular cytokine staining for a comparative measurement of cellular immune responses in hiv-1 and hiv-2 infections in west africa.an efficient and quantitative tool for rapid assessment of human immunodeficiency virus (hiv)-induced cellular immune responses is important for resource-limited settings, such as in sub-saharan africa. modifications are required to previously reported methods for evaluating ex-vivo antigen-specific cellular responses based on direct recombinant vaccinia virus (rvv) stimulation of peripheral blood mononuclear cells (pbmcs) by enzyme linked immunosorbent assay (elispot) and by flow cytometry intr ...200617100767
nitroimidazoles, part 2: synthesis, antiviral and antitumor activity of new 4-nitroimidazoles.a series of 5-alkylamino and 5-alkylsulfanyl derivatives of 1-aryl-2-alkyl-4-nitro-1h-imidazoles 12-21, 31, and 34 were synthesized by a simple method with the aim to develop novel hiv non-nucleoside reverse transcriptase inhibitors (nnrtis). all the new compounds were tested against hiv-1 and hiv-2 in mt-4 cells. compound 21, with an arylsulfanyl group at c(5) of the 4-nitro-1h-imidazole backbone showed an ec(50) value of 0.22 microg/ml against hiv-1 with a therapeutic index of 13. this means t ...200617193287
protective immunity against hiv infection: lessons from hiv-2 infection.despite two decades of intensive research, the correlates of protective immunity to hiv-1 infection remain elusive. much less attention has been paid to the related human virus strain, hiv-2, which can cause aids, but does not usually do so in the majority of infected people. what can be learned from hiv-2 infection about how the human host can peacefully coexist with a pathogenic retrovirus?200617661633
natural polymorphisms of hiv type 2 pol sequences from drug-naive individuals.until today, the susceptibility of human immunodeficiency virus type 2 (hiv-2) to protease and nucleosidic reverse-transcriptase inhibitors (pi and nrti, respectively) has not been clearly documented. in this report we studied hiv-2 proviral sequences (n = 30) from drug-naive patients. our results revealed that several amino acid positions in the protease and reverse transcriptase coding sequence harbored residues that have been associated with drug resistance in hiv-1-infected patients. in part ...200617147507
nfat5 regulates hiv-1 in primary monocytes via a highly conserved long terminal repeat site.to replicate, hiv-1 capitalizes on endogenous cellular activation pathways resulting in recruitment of key host transcription factors to its viral enhancer. rna interference has been a powerful tool for blocking key checkpoints in hiv-1 entry into cells. here we apply rna interference to hiv-1 transcription in primary macrophages, a major reservoir of the virus, and specifically target the transcription factor nfat5 (nuclear factor of activated t cells 5), which is the most evolutionarily diverg ...200617173480
false-positive result of a confirmatory human immunodeficiency virus line immuno assay in an apparently healthy individual--a case report.a case of a false-positive result of human immunodeficiency virus (hiv) confirmatory immunoblot-based assay is described. repeatedly borderline reactive anti-hiv screening enzyme immunoassay result obtained in a local hospital resulted in directing the sample to the slovenian hiv/aids reference laboratory. in the reference laboratory, both anti-hiv screening assays and confirmatory western blot were negative, while a confirmatory test inno-lia hiv i/ii score (innogenetics, ghent, belgium) was an ...200617508473
hydrophilicity dependent budding and secretion of chimeric hiv gag-v3 virus-like particles.virus-like particles (vlps) of numerous viruses have been considered as possible candidates for vaccine development. we have constructed hiv chimeric genes by coupling the gag gene of hiv-2 with the v3 domain of the gp120 gene of either hiv-1 or hiv-2 and expressed the chimeric genes in sf21 cells using the recombinant baculovirus expression system. although the level of expression of the chimeric hiv-2 gag gene with the v3 domain of either hiv-1 gp120 (gagc-1v3) or hiv-2 gp120 (gagc-2v3) was hi ...200717510784
study on the blood-borne virus co-infection and t lymphocyte subset among intravenous drug users.to investigate the features of various blood-borne virus infections and co-infection in intravenous drug users (idus), and to examine the correlation of t lymphocyte subsets with virus co-infection.200717511038
[hiv-2 infection and human lymphotropic type 1 and type 2 virus in spain]. 200717570181
in vitro selection and characterization of human immunodeficiency virus type 2 with decreased susceptibility to lopinavir.lopinavir (lpv)-ritonavir has demonstrated durable antiviral activity in human immunodeficiency virus type 1 (hiv-1)-infected antiretroviral-naïve and protease inhibitor (pi)-experienced patients. however, information on lpv activity against hiv-2 and the patterns of mutations in hiv-2 in response to selection by lpv is limited. the activity of lpv against three strains of hiv-2 was assessed and compared to activity against a reference hiv-1 strain. lpv demonstrated activity similar to that obse ...200717576848
role of human immunodeficiency virus (hiv)-specific t-cell immunity in control of dual hiv-1 and hiv-2 infection.progressive immune dysfunction and aids develop in most cases of human immunodeficiency virus type 1 (hiv-1) infection but in only 25 to 30% of persons with hiv-2 infection. however, the natural history and immunologic responses of individuals with dual hiv-1 and hiv-2 infection are largely undefined. based on our previous findings, we hypothesized that among patients with dual infection the control of hiv-1 is associated with the ability to respond to hiv-2 gag epitopes and to maintain hiv-spec ...200717582003
monitoring the dynamics of the hiv epidemic using assays for recent infection and serotyping among new hiv diagnoses: experience after 2 years in france.new tools to better monitor dynamics of human immunodeficiency virus (hiv) transmission are needed.200717597452
defect of human immunodeficiency virus type 2 gag assembly in saccharomyces cerevisiae.we have previously shown that the expression of human immunodeficiency virus type 1 (hiv-1) gag protein in saccharomyces cerevisiae spheroplasts produces gag virus-like particles (vlps) at the plasma membrane, indicating that yeast has all the host factors necessary for hiv-1 gag assembly. here we expand the study by using diverse primate lentiviral gags and show that yeast does not support the production of hiv-2 or simian immunodeficiency virus sivmac gag vlps but allows the production of siva ...200717609278
replication-competent variants of human immunodeficiency virus type 2 lacking the v3 loop exhibit resistance to chemokine receptor antagonists.entry of human immunodeficiency virus type 1 (hiv-1) and hiv-2 requires interactions between the envelope glycoprotein (env) on the virus and cd4 and a chemokine receptor, either ccr5 or cxcr4, on the cell surface. the v3 loop of the hiv gp120 glycoprotein plays a critical role in this process, determining tropism for ccr5- or cxcr4-expressing cells, but details of how v3 interacts with these receptors have not been defined. using an iterative process of deletion mutagenesis and in vitro adaptat ...200717609282
the origins of hiv and implications for the global epidemic.hiv type 1 (hiv-1) and type 2 (hiv-2) are the result of several cross-species transmissions from primates to humans. recently, the ancestral strains of hiv-1 groups m and n were shown to still persist in today's wild chimpanzee populations (pan troglodytes troglodytes) in south cameroon. lately, hiv-1 group o-related viruses have been identified in western gorillas (gorilla gorilla), called sivgor, but chimpanzees are most likely the original reservoir of this simian immunodeficiency virus (siv) ...200717618555
the hiv1 protein vpr acts to promote g2 cell cycle arrest by engaging a ddb1 and cullin4a-containing ubiquitin ligase complex using vprbp/dcaf1 as an adaptor.the roles of the hiv1 protein vpr in virus replication and pathogenesis remain unclear. expression of vpr in dividing cells causes cell cycle arrest in g(2). vpr also facilitates low titer infection of terminally differentiated macrophages, enhances transcription, promotes apoptosis, and targets cellular uracil n-glycosylase for degradation. using co-immunoprecipitation and tandem mass spectroscopy, we found that hiv1 vpr engages a ddb1- and cullin4a-containing ubiquitin-ligase complex through v ...200717620334
aptamer displacement identifies alternative small-molecule target sites that escape viral resistance.aptamers targeting reverse transcriptase (rt) from hiv-1 inhibit viral replication in vitro, presumably by competing with binding of the primer/template complex. this site is not targeted by the currently available small-molecule anti-hiv-1 rt inhibitors. we have identified sy-3e4, a small-molecule inhibitor of hiv-1 rt, by applying a screening assay that utilizes a reporter-ribozyme regulated by the anti-hiv-1 rt aptamer. sy-3e4 displaces the aptamer from the protein, selectively inhibits dna-d ...200717656317
chimeric hiv-1 and hiv-2 lentiviral vectors with added safety insurance.lentiviruses are unique in their ability to infect both dividing and non-dividing cells. this makes the vectors derived from them particularly useful for gene transfer into non-dividing cells, including stem cells. lentiviral vectors are becoming the vectors of choice for si/shrna delivery. the utility of the lentiviral vectors will be enhanced if additional elements of safety are built into their design. one safety concern is the generation of replication competent virus by recombination. we re ...200717177309
adaptation of a diverse simian immunodeficiency virus population to a new host is revealed through a systematic approach to identify amino acid sites under selection.simian immunodeficiency viruses (siv) have had considerable success at crossing species barriers; both human immunodeficiency virus (hiv)-1 and hiv-2 have been transmitted on multiple occasions from siv-infected natural host species. however, the precise evolutionary and ecological mechanisms characterizing a successful cross-species transmission event remain to be elucidated. here, in addition to expanding and clarifying our previous description of the adaptation of a diverse, naturally occurri ...200717159231
antiviral activity obtained from aqueous extracts of the chilean soapbark tree (quillaja saponaria molina).natural, aqueous extracts of quillaja saponaria, the chilean soapbark tree, contain several physiologically active triterpenoid saponins that display strong adjuvant activity when used in either human or animal vaccines. in this paper, we describe studies that demonstrate a novel antiviral activity of quillaja extracts against six viruses: vaccinia virus, herpes simplex virus type 1, varicella zoster virus, human immunodeficiency viruses 1 and 2 (hiv-1, hiv-2) and reovirus. we demonstrate that m ...200717170461
inhibition of human immunodeficiency virus type 1 transcription by n-aminoimidazole derivatives.this study describes the mechanism of antiviral action of the n-aminoimidazole derivatives which exclusively inhibit retroviruses such as hiv-1, hiv-2, siv and msv. these antiretroviral compounds, with lead prototype nr-818, were found to inhibit hiv-1 replication at the transcriptional level. analysis of each individual step of viral transcription, including transcriptional activation mediated by nf-kappab, the chromatin remodeling process at the viral promoter and viral mrna transcription medi ...200717459445
a single amino acid of the human immunodeficiency virus type 2 capsid affects its replication in the presence of cynomolgus monkey and human trim5alphas.human immunodeficiency virus type 2 (hiv-2) strains vary widely in their abilities to grow in old world monkey (owm) cells such as those of cynomolgus monkeys (cm). we evaluated eight hiv-2 isolates for their sensitivities to cm trim5alpha, an anti-hiv factor in owm cells. we found that different hiv-2 isolates showed differences in their sensitivities to cm trim5alpha. sequence analysis showed that trim5alpha-sensitive viruses had proline at the 120th position of the capsid protein (ca), wherea ...200717475650
virus subtype-specific features of natural simian immunodeficiency virus sivsmm infection in sooty mangabeys.simian immunodeficiency virus (siv) siv(smm) naturally infects sooty mangabeys (sms) and is the source virus of pathogenic infections with human immunodeficiency virus type 2 (hiv-2) and siv(mac) of humans and macaques, respectively. in previous studies we characterized siv(smm) diversity in naturally siv-infected sms and identified nine different phylogenetic subtypes whose genetic distances are similar to those reported for the different hiv-1 group m subtypes. here we report that, within the ...200717507488
the impact of hiv status and type on the clearance of human papillomavirus infection among senegalese women.persistent infection with human papillomavirus (hpv) is associated with the development and progression of hpv-related disease, including cervical intraepithelial neoplasia (cin) and invasive cervical cancer.200717703420
evaluation of the murex hiv ag/ab combination assay when used with dried blood spots.this study evaluated the ability of the murex hiv ag/ab combination assay to detect human immunodeficiency virus (hiv) antibodies in 12 617 dried blood spots (dbss) on filter paper. the assay had an overall sensitivity of 99.6% and a specificity of 99.9%. in view of its ability to detect p24 antigen and both hiv-1 and hiv-2 antibodies in samples collected in the form of dbss, the murex ag/ab combination assay is suitable for use as a standard screening assay for seroprevalence studies, as well a ...200717725648
efficient thymopoiesis contributes to the maintenance of peripheral cd4 t cells during chronic human immunodeficiency virus type 2 infection.human immunodeficiency virus type 2 (hiv-2) infection leads to a lifelong asymptomatic period in the majority of patients. even in patients with progressive disease, a slow cd4 count decline characterizes the chronic phase of hiv-2 infection, suggesting that peripheral t-cell homeostasis is controlled better following hiv-2 infection than following hiv-1 infection. herein we showed that, in contrast to hiv-1-infected patients, hiv-2-infected patients demonstrate enhanced thymic function compared ...200717804512
programmed ribosomal frameshifting in siv is induced by a highly structured rna stem-loop.simian immunodeficiency virus (siv), like its human homologues (hiv-1, hiv-2), requires a -1 translational frameshift event to properly synthesize all of the proteins required for viral replication. the frameshift mechanism is dependent upon a seven-nucleotide slippery sequence and a downstream rna structure. in siv, the downstream rna structure has been proposed to be either a stem-loop or a pseudoknot. here, we report the functional, structural and thermodynamic characterization of the siv fra ...200717868691
dendritic cells are less susceptible to human immunodeficiency virus type 2 (hiv-2) infection than to hiv-1 infection.human immunodeficiency virus type 1 (hiv-1) infection of dendritic cells (dcs) has been documented in vivo and may be an important contributor to hiv-1 transmission and pathogenesis. hiv-1-specific cd4(+) t cells respond to hiv antigens presented by hiv-1-infected dcs and in this process become infected, thereby providing a mechanism through which hiv-1-specific cd4(+) t cells could become preferentially infected in vivo. hiv-2 disease is attenuated with respect to hiv-1 disease, and host immune ...200717913821
isothiazole derivatives as antiviral agents.we recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile and s-(4-cyano-5-phenylisothiazol -3-yl)-o-ethyl thiocarbonate, which were found to be effective against both hiv-1 (iiib) and hiv-2 (rod). we have now evaluated these compounds against both rna and dna viruses, obtaining high selectivity indexes for poliovirus 1 (si: 223 and 828, respectively) and echovirus 9 (si: 334 and 200, respectivel ...200718046960
nef-mediated enhancement of virion infectivity and stimulation of viral replication are fundamental properties of primate lentiviruses.nef is a multifunctional accessory protein of primate lentiviruses. recently, it has been shown that the ability of nef to downmodulate cd4, cd28, and class i major histocompatibility complex is highly conserved between most or all primate lentiviruses, whereas nef-mediated downregulation of t-cell receptor-cd3 was lost in the lineage that gave rise to human immunodeficiency virus type 1 (hiv-1). whether or not other nef activities are preserved between different groups of primate lentiviruses r ...200717928336
detection of emerging hiv variants in blood donors from urban areas of cameroon.the u.s. food and drug administration has licensed several assays for use in donor testing and management of persons with human immunodeficiency virus (hiv) infection. however, the performance of these assays for detection and quantitation of emerging hiv genetic variants has not been studied extensively. we tested 240 human plasma specimens collected from two urban blood centers in cameroon where hiv genetic diversity and recombinant hiv strains are highly prevalent, using several fda licensed ...200717961114
[evaluation of new fourth-generation human immunodeficiency virus antigen and antibody detection assay with enzyme-linked fluorescent immunoassay].we evaluated the fourth-generation hiv screening assay vidas hiv duoii (duoii) based on elfa for simultaneous detection of anti-hiv-1 and anti-hiv-2 antibodies and hiv-1 p24 antigen through comparison with other hiv antigen-antibody detection assays. materials were 1228 hiv-negative specimens, 95 hiv-antibody-positive specimens, and hiv commercial panels. the specificity of duoii was 99.8% and sensitivity 100%, detecting all of hiv-1 group m subtype a, b, b', c, d, a/e, f, g, b/d, hiv-1 group o, ...200717966638
rna recognition mechanism of the minimal active domain of the human immunodeficiency virus type-2 nucleocapsid protein.ncp8 of hiv-2 contains two cchc-type zinc fingers connected by a linker, and is involved in many critical steps of the virus life cycle. it was previously shown that the first zinc finger flanked by the linker is the minimal active domain for specific binding to viral rna. in our previous study, we determined the three-dimensional structure of ncp8-f1, including the minimal active domain, and found that a hydrogen bond between asn(11) n(delta)h and arg(27) o stabilized the conformation of the li ...200717202191
an extended stem-loop 1 is necessary for human immunodeficiency virus type 2 replication and affects genomic rna encapsidation.genomic rna encapsidation in lentiviruses is a highly selective and regulated process. the unspliced rna molecules are selected for encapsidation from a pool of many different viral and cellular rna species. moreover, two molecules are encapsidated per viral particle, where they are found associated as a dimer. in this study, we demonstrate that a 10-nucleotide palindromic sequence (pal) located at the 3' end of the psi encapsidation signal is critical for human immunodeficiency virus type 2 (hi ...200717229705
modest human immunodeficiency virus coreceptor function of cxcr3 is strongly enhanced by mimicking the cxcr4 ligand binding pocket in the cxcr3 receptor.the chemokine receptor cxcr3 can exhibit weak coreceptor function for several human immunodeficiency virus type 1 (hiv-1) and hiv-2 strains and clinical isolates. these viruses produced microscopically visible cytopathicity in u87.cd4.cxcr3 cell cultures, whereas untransfected (cxcr3-negative) u87.cd4 cells remained uninfected. depending on the particular virus, the coreceptor efficiency of cxcr3 was 100- to >10,000-fold lower compared to that of cxcr4. a cxcr3 variant carrying the cxcr4 binding ...200717251291
long-term intrapatient viral evolution during hiv-2 infection.background. disease progression and transmission of human immunodeficiency virus (hiv) type 2 are attenuated, compared with hiv-1, which is consistent with the lower plasma viral loads observed in hiv-2 infection. although numerous studies have characterized the intrapatient evolution of viral sequences during hiv-1 infection, prospective studies examining intrapatient evolution during hiv-2 infection have been limited.methods. we examined viral sequence evolution in the c2v3c3 region of the vir ...200717262716
efficient transduction of simian cells by hiv-1-based lentiviral vectors that contain mutations in the capsid protein.recently, the cyclophilin a (cypa)-binding region of the hiv-1 capsid protein was identified as a viral determinant involved in the post-entry restriction in old world monkey cells. here, we constructed a panel of hiv-1-based lentiviral vectors (lvs) that contain either mutations in the cypa-binding region or the cypa-binding region of the related viruses hiv-1 group o and hiv-2. we demonstrated that amino-acid changes in the cypa-binding region of the capsid can alter the phenotype of the virus ...200717299408
comparison of heterologous neutralizing antibody responses of human immunodeficiency virus type 1 (hiv-1)- and hiv-2-infected senegalese patients: distinct patterns of breadth and magnitude distinguish hiv-1 and hiv-2 infections.neutralizing antibody responses against heterologous isolates in human immunodeficiency virus type 1 (hiv-1) and hiv-2 infections were compared, and their relationships with established clinical markers of progression were examined. neutralizing responses against 7 heterologous primary isolates and 1 laboratory strain were compared between 32 untreated hiv-1-infected subjects and 35 untreated hiv-2-infected subjects using a pseudotyped reporter virus assay. the breadth of the neutralizing respon ...200717301136
molecular mechanisms of simian immunodeficiency virus siv(agm) rna encapsidation.primate lentiviruses are composed of several distinct lineages, including human immunodeficiency virus type 1 (hiv-1), hiv-2, and simian immunodeficiency virus sivagm. hiv-1 and hiv-2 have significant differences in the mechanisms of viral rna encapsidation. therefore, the rna packaging mechanisms of sivagm cannot be predicted from the studies of hiv-1 and hiv-2. we examined the roles of the nucleocapsid (nc) zinc finger motifs on rna packaging by mutating the conserved zinc finger (cchc) motifs ...200717321560
cross-clade inhibition of recombinant human immunodeficiency virus type 1 (hiv-1), hiv-2, and simian immunodeficiency virus sivcpz reverse transcriptases by rna pseudoknot aptamers.reverse transcriptase (rt) remains a primary target in therapies directed at human immunodeficiency virus type 1 (hiv-1). rna aptamers that bind rt from hiv-1 subtype b have been shown to protect human cells from infection and to reduce viral infectivity, but little is known about the sensitivity of the inhibition to amino sequence variations of the rt target. therefore, we assembled a panel of 10 recombinant rts from phylogenetically diverse lentiviral isolates (including strains of hiv-1, simi ...200717329328
direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (hiv-2) infection than in hiv-1 infection.studies have shown that human immunodeficiency virus type 2 (hiv-2) is less pathogenic than hiv-1, with a lower rate of disease progression. similarly, plasma viral loads are lower in hiv-2 infection, suggesting that hiv-2 replication is restricted in vivo in comparison to that of hiv-1. however, to date, in vivo studies characterizing replication intermediates in the viral life cycle of hiv-2 have been limited. in order to test the hypothesis that hiv-2 has a lower replication rate in vivo than ...200717329334
development and evaluation of an oligonucleotide ligation assay for detection of drug resistance-associated mutations in the human immunodeficiency virus type 2 pol gene.human immunodeficiency virus type 2 (hiv-2) is naturally resistant to several antiretroviral drugs, including all of the non-nucleoside reverse transcriptase inhibitors and the entry inhibitor t-20, and may have reduced susceptibility to some protease inhibitors. these resistance properties make treatment of hiv-2 patients difficult, with very limited treatment options. therefore, early detection of resistance mutations is important for understanding treatment failures and guiding subsequent the ...200717329450
mechanisms of cd4 downregulation by the nef and vpu proteins of primate immunodeficiency viruses.human immunodeficiency virus type 1 (hiv-1), human immunodeficiency virus type 2 (hiv-2), and simian immunodeficiency virus (siv) are the etiological agents of acquired immunodeficiency syndrome (aids) in humans and a related disease in non-human primates. these viruses infect t cells and macrophages that express the surface glycoprotein, cd4, because this glycoprotein acts as a co-receptor for incoming virus particles. once infection has occurred, however, the presence of cd4 poses problems for ...200717346169
mechanism and history of evolution of symbiotic hiv strains into lethal pandemic strains: the key event may have been a 1927 trial of pamaquine in leopoldville (kinshasa), congo.in previous papers, i have rejected both the zoonosis and the serial transfer hypotheses of the origin and evolution of the current lethal pandemic strains of hiv. the hypothesis that fits the critical observations is that all the human and nonhuman primate species in central africa (an area of hyper-endemic malaria) have shared (through inter-species transfers) a "primate t-cell retrovirus" (ptrv), which has adapted to each host species. this retrovirus is believed to assist primate t-cells att ...200717368749
a novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (pi), grl-98065, is potent against multiple-pi-resistant human immunodeficiency virus in vitro.we designed, synthesized, and identified grl-98065, a novel nonpeptidic human immunodeficiency virus type 1 (hiv-1) protease inhibitor (pi) containing the structure-based designed privileged cyclic ether-derived nonpeptide p2 ligand, 3(r),3a(s),6a(r)-bis-tetrahydrofuranylurethane (bis-thf), and a sulfonamide isostere, which is highly potent against laboratory hiv-1 strains and primary clinical isolates (50% effective concentration [ec(50)], 0.0002 to 0.0005 microm) with minimal cytotoxicity (50% ...200717371811
out of africa: what can we learn from hiv-2 about protective immunity to hiv-1?most people infected with human immunodeficiency virus 2 (hiv-2) do not progress to disease, even though the minority who do cannot be distinguished clinically from hiv-1-infected patients. here we review what is known about the basis of viral control in hiv-2 infection.200717375091
dissecting the neutralizing antibody specificities of broadly neutralizing sera from human immunodeficiency virus type 1-infected donors.attempts to elicit broadly neutralizing antibody responses by human immunodeficiency virus type 1 (hiv-1) vaccine antigens have been met with limited success. to better understand the requirements for cross-neutralization of hiv-1, we have characterized the neutralizing antibody specificities present in the sera of three asymptomatic individuals exhibiting broad neutralization. two individuals were infected with clade b viruses and the third with a clade a virus. the broadly neutralizing activit ...200717409160
characterization of hiv-1 integrase n-terminal mutant viruses.during infection, human immunodeficiency virus type 1 integrase engages a number of molecules and mechanisms, both of viral and cellular origin. in one of such instances, integrase is thought to be degraded by the n-end rule proteasome pathway a process that targets the n-terminal residue of its substrates. here we describe the properties of hiv-1 viruses in which the first amino acid residue of integrase has been substituted to render it resistant to the n-end rule pathway. as result of this ex ...200717109911
natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors.human immunodeficiency virus type 2 (hiv-2) contains numerous natural polymorphisms in its protease (pr) gene that are implicated in drug resistance in the case of hiv-1. this study evaluated emergent pr resistance in hiv-2. three hiv-2 isolates were selected for resistance to amprenavir (apv), nelfinavir (nfv), indinavir (idv), and tipranavir (tpv) in cell culture. genotypic analysis determined the time to the appearance of protease inhibitor (pi)-associated mutations compared to hiv-1. phenoty ...200717116674
the sivmac239 pr55gag isoform, siv p43, suppresses proteolytic cleavage of pr55gag.in human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus (siv) the gag gene encodes the precursor polyprotein pr55gag, which is cleaved by the viral protease to produce the major structural proteins. recently, it has been shown that hiv and siv gag rnas contain internal ribosome entry sites (iress) that mediate translation of pr55gag [pr57gag in hiv type 2 (hiv-2)] isoforms. previously, we demonstrated that sivmac239 p43(-), a mutant that does not express the pr55gag isof ...200717092530
quantitative detection of plasma human immunodeficiency virus type 2 subtype a rna by the nuclisens easyq assay (version 1.1).no commercial viral load assay has yet been approved for use for measurement of human immunodeficiency virus type 2 (hiv-2) rna levels in plasma. we assessed the performance of the nuclisens easyq (version 1.1) assay (easyq; biomérieux, boxtel, the netherlands) to quantify hiv-2 viremia. a viral stock was prepared from an hiv-2 (subtype a)-infected patient. culture supernatant was subjected to viral particle counting by electron microscopy. serial dilutions of the viral stock were made in hiv-ne ...200717093034
a hiv-2-based self-inactivating vector for enhanced gene transduction.the employment of hiv-1-based vectors in clinical trials is controversial mainly due to the lethal nature of the virus. hiv-2 is less pathogenic in nature and therefore is likely to be safer for vector design and production. we developed hiv-2-based self-inactivating vectors in which 520 bp out of 554 bp of the viral u3 was deleted. interestingly, high titers were obtained only when an exogenous promoter was used to drive expression of viral rna. it was found that the vectors could target a wide ...200716979253
dimerisation of hiv-2 genomic rna is linked to efficient rna packaging, normal particle maturation and viral infectivity.retroviruses selectively encapsidate two copies of their genomic rna, the gag protein binding a specific rna motif in the 5' utr of the genome. in human immunodeficiency virus type 2 (hiv-2), the principal packaging signal (psi) is upstream of the major splice donor and hence is present on all the viral rna species. cotranslational capture of the full length genome ensures specificity. hiv-2 rna dimerisation is thought to occur at the dimer initiation site (dis) located in stem-loop 1 (sl-1), do ...200718078509
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