Publications

TitleAbstractYear
Filter
PMID
Filter
hiv type 1 infection of plasmacytoid and myeloid dendritic cells is restricted by high levels of samhd1 and cannot be counteracted by vpx.dendritic cells are professional antigen-presenting cells of the immune system and are major producers of type-i interferon. their role in hiv-1 infection is not well understood. they express cd4 and ccr5 yet appear to be resistant to infection. in culture, infection of the cells with hiv-1 is inhibited by the host cell restriction factor samhd1. lentiviruses such as hiv-2/sivmac counteract the restriction by encoding vpx, a virion-packaged accessory protein that induces the proteasomal degradat ...201423924154
increased hot flash severity and related interference in perimenopausal human immunodeficiency virus-infected women.as women with human immunodeficiency virus (hiv) are living longer, more are entering perimenopause. prior studies suggest that hiv-infected women are more likely to have hot flashes than non-hiv-infected women. however, little is known regarding hot flash severity and hot flash-related interference with daily function, mood, and quality of life in this population.201423820600
electrochemical enzyme-linked immunosorbent assay featuring proximal reagent generation: detection of human immunodeficiency virus antibodies in clinical samples.we describe a simple electrochemical immunoassay for human immunodeficiency virus (hiv) antibody detection that localizes capture and detection reagents in close proximity to a microelectrode. antigenic peptides from hiv-1 gp41 or hiv-2 gp36 were covalently attached to a su-8 substrate that also presented a template for the deposition of three-dimensional microelectrodes. the detection of hiv antibodies was achieved with an electrochemical immunoassay where an alkaline phosphatase conjugated sec ...201323758505
large-scale graphene micropattern nano-biohybrids: high-performance transducers for fet-type flexible fluidic hiv immunoassays.large-scale fet-type graphene micropattern (gm) nano-biohybrid-based immunosensor (gmns) is fabricated in a controlled fashion to detect human immunodeficiency virus 2 antibody. flexible gmns shows a highly sensitive response and excellent mechanical bendability. the flexible gmns in fluidic systems also has a stable response. this is the first experimental demonstration of a large-scale flexible fluidic fet-type immunoassay based on gm nano-biohybrids.201323744620
anti-hiv host factor samhd1 regulates viral sensitivity to nucleoside reverse transcriptase inhibitors via modulation of cellular deoxyribonucleoside triphosphate (dntp) levels.newly identified anti-hiv host factor, samhd1, restricts replication of lentiviruses such as hiv-1, hiv-2, and simian immunodeficiency virus in macrophages by enzymatically hydrolyzing and depleting cellular dntps, which are the substrates of viral dna polymerases. hiv-2 and some simian immunodeficiency viruses express viral protein x (vpx), which counteracts samhd1 and elevates cellular dntps, enhancing viral replication in macrophages. because nucleoside reverse transcriptase inhibitors (nrtis ...201323744077
laboratory diagnosis of hiv in adults: a review of current methods.of the estimated 1.2 million people infected with human immunodeficiency virus (hiv) in the united states, 20% are unaware of their diagnosis. improved methods of hiv testing could decrease this number, as well as identify those who have recently acquired hiv infection and are at the most critical stage of infectivity. people with acute hiv infection have demonstrated enhanced transmission of hiv in multiple epidemiologic and pathogenetic studies. more than 50 000 hiv infections occur annually i ...201323667267
high level of susceptibility to human trim5α conferred by hiv-2 capsid sequences.hiv-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from hiv-1 in its infectivity, transmissibility and pathogenicity. we have tested the possibility that a greater susceptibility of hiv-2 capsid (ca) to the human restriction factor trim5α (htrim5α) could contribute to these differences.201323647667
the hiv-2 rev-response element: determining secondary structure and defining folding intermediates.interaction between the viral protein rev and the rna motifs known as rev response elements (rres) is required for transport of unspliced and partially spliced human immunodeficiency virus (hiv)-1 and hiv-2 rnas from the nucleus to the cytoplasm during the later stages of virus replication. a more detailed understanding of these nucleoprotein complexes and the host factors with which they interact should accelerate the development of new antiviral drugs targeting cis-acting rna regulatory signal ...201323640333
an hiv type 2 case series in italy: a phylogenetic analysis.in recent years, the increase of migration from countries where human immunodeficiency virus type 2 (hiv-2) is endemic to industrialized countries has facilitated the spread of the virus in individuals previously unexposed to this threat. in this report, we performed a phylogenetic analysis on pol and env sequences of hiv-2 strains identified in foreigners and native citizens to trace the origin of infection. all but one of the 17 pol gene sequences were classified as group a. hiv-2 strains were ...201323638670
platelet activation suppresses hiv-1 infection of t cells.platelets, anucleate cell fragments abundant in human blood, can capture hiv-1 and platelet counts have been associated with viral load and disease progression. however, the impact of platelets on hiv-1 infection of t cells is unclear.201323634812
a novel anti-hiv active integrase inhibitor with a favorable in vitro cytochrome p450 and uridine 5'-diphospho-glucuronosyltransferase metabolism profile.research efforts on the human immunodeficiency virus (hiv) integrase have resulted in two approved drugs. however, co-infection of hiv with mycobacterium tuberculosis and other microbial and viral agents has introduced added complications to this pandemic, requiring favorable drug-drug interaction profiles for antiviral therapeutics targeting hiv. cytochrome p450 (cyp) and uridine 5'-diphospho-glucuronosyltransferase (ugt) are pivotal determining factors in the occurrence of adverse drug-drug in ...201323602851
transient expansion of activated cd8(+) t cells characterizes tuberculosis-associated immune reconstitution inflammatory syndrome in patients with hiv: a case control study.cd4(+) t cell activation indicators have been reported to be a common phenomenon underlying diverse manifestations of immune reconstitution inflammatory syndrome (iris). however, we have found that a high frequency of circulating cd8(+) t cells is a specific risk factor for mycobacterial iris. therefore, we investigated whether cd8(+) t cells from patients who develop tb iris were specifically activated.201323688318
restriction of retroviral infection of macrophages.primate immunodeficiency viruses are highly specialized lentiviruses that have evolved to successfully infect and persist for the lifetime of the host. despite encountering numerous potent antiviral factors, hivs and sivs are successful pathogens due to the acquisition of equally potent countermeasures in the form of accessory genes. the accessory gene vpx encoded by hiv-2 and a subset of sivs have a profound effect on the ability of lentiviruses to infect non-dividing cells, such as macrophages ...201323686233
hiv-2 and sivmac accessory virulence factor vpx down-regulates samhd1 enzyme catalysis prior to proteasome-dependent degradation.samhd1, a dgtp-regulated deoxyribonucleoside triphosphate (dntp) triphosphohydrolase, down-regulates dntp pools in terminally differentiated and quiescent cells, thereby inhibiting hiv-1 infection at the reverse transcription step. hiv-2 and simian immunodeficiency virus (siv) counteract this restriction via a virion-associated virulence accessory factor, vpx (vpr in some sivs), which loads samhd1 onto crl4-dcaf1 e3 ubiquitin ligase for polyubiquitination, programming it for proteasome-dependent ...201323677995
restriction of diverse retroviruses by samhd1.samhd1 is a triphosphohydrolase that restricts the replication of hiv-1 and siv in myeloid cells. in macrophages and dendritic cells, samhd1 restricts virus replication by diminishing the deoxynucleotide triphosphate pool to a level below that which supports lentiviral reverse transcription. hiv-2 and related sivs encode the accessory protein vpx to induce the proteasomal degradation of samhd1 following virus entry. while samhd1 has been shown to restrict hiv-1 and siv, the breadth of its restri ...201323497255
hiv-2 and its role in conglutinated approach towards acquired immunodeficiency syndrome (aids) vaccine development.acquired immunodeficiency syndrome (aids) is one of the most critically acclaimed endemic diseases, caused by two lentiviruses hiv-1 and 2. hiv-2 displays intimate serological and antigenic resemblance to simian immunodeficiency virus (siv) along with less pathogenicity, lower infectivity and appreciable cross reactivity with hiv-1 antigens. the present era is confronted with the challenge to fabricate a vaccine effective against all clades of both the species of hiv. but vaccine development aga ...201323483108
monocyte and myeloid dendritic cell activation occurs throughout hiv type 2 infection, an attenuated form of hiv disease.monocytes and myeloid dendritic cells (mdcs) are important orchestrators of innate and human immunodeficiency virus (hiv)-specific immune responses and of the generalized inflammation that characterizes aids progression. to our knowledge, we are the first to investigate monocyte and mdc imbalances in hiv type 2 (hiv-2)-positive patients, who typically feature reduced viremia and slow disease progression despite the recognized ability of hiv-2 to establish viral reservoirs and overcome host restr ...201323460749
when phylogenetic analysis complements the epidemiological investigation: a case of hiv-2 infection, italy.human immunodeficiency virus type 2 (hiv-2) infection is geographically restricted, affecting west african countries such as guinea- bissau and cape verde. we describe a recent case of hiv-2 infection in an italian patient. phylogenetic analysis of the v3 region of hiv-2 indicated that the italian patient was infected by hiv-2 subtype a2. the sequence obtained from the italian patient clustered significantly with a sequence isolated from senegal. a phylogenetic doubt may arise from a guinea biss ...201323435822
hiv-2eu: supporting standardized hiv-2 drug resistance interpretation in europe.considering human immunodeficiency virus type 2 (hiv-2) phenotypic data and experience from hiv type 1 and from the follow-up of hiv-2-infected patients, a panel of european experts voted on a rule set for interpretation of mutations in hiv-2 protease, reverse transcriptase, and integrase and an automated tool for hiv-2 drug resistance analyses freely available on the internet (http://www.hiv-grade.de).201323429380
tetramerization of samhd1 is required for biological activity and inhibition of hiv infection.samhd1 is a dgtp-activated dntpase that has been implicated as a modulator of the innate immune response. in monocytes and their differentiated derivatives, as well as in quiescent cells, samhd1 strongly inhibits hiv-1 infection and, to a lesser extent, hiv-2 and simian immunodeficiency virus (siv) because of their virion-associated virulence factor vpx, which directs samhd1 for proteasomal degradation. here, we used a combination of biochemical and virologic approaches to gain insights into the ...201323426366
[molecular epidemiological analysis of hiv-1 pol gene sequences isolated in istanbul, turkey].human immunodeficiency virus (hiv) characterized by a high genetic variability includes two genotypes namely hiv-1 and hiv-2. a major proportion of the infections worldwide is caused by hiv-1 which includes four groups (m, n, o and p). group m being responsible for the hiv pandemic is further divided into nine genetically distinct subtypes (a, b, c, d, f, g, h, j, and k). additionally, more than 49 circulating recombinant forms (crfs) have been recognized up to now. the aim of this study was to ...201323390906
host iron redistribution as a risk factor for incident tuberculosis in hiv infection: an 11-year retrospective cohort study.identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (hiv) infection may improve clinical management of co-infections. iron influences tuberculosis (tb) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, tb will develop. the objective of this res ...201323360117
novel factors interfering with human immunodeficiency virus-type 1 replication in vivo and in vitro.the strategy of all retroviral infections is based on establishing an equilibrium between virus replication and proviral latency in the infected host. the human immunodeficiency virus-type 1 (hiv-1), belonging to the subfamily of lentiviridae, adds an additional level of sophistication to this general rule by encoding two regulatory genes (tat and rev) and four accessory genes (nef, vif, vpr and vpu); hiv-2, structurally similar to hiv-1 but characterized by lower pathogenicity in vivo, encodes ...201323330719
adaptation to the interferon-induced antiviral state by human and simian immunodeficiency viruses.the production of type i interferon (ifn) is an early host response to different infectious agents leading to the induction of hundreds of ifn-stimulated genes (isgs). the roles of many isgs in host defense are unknown, but their expression results in the induction of an "antiviral state" that inhibits the replication of many viruses. here we show that prototype primate lentiviruses human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus of macaques (siv(mac) and siv(mne)) ...201323325684
an ancestral hiv-2/simian immunodeficiency virus peptide with potent hiv-1 and hiv-2 fusion inhibitor activity.to produce new fusion inhibitor peptides for hiv-1 and hiv-2 based on ancestral envelope sequences.201323324659
evidence for a different susceptibility of primate lentiviruses to type i interferons.type i interferons induce a complex transcriptional program that leads to a generalized antiviral response against a large panel of viruses, including human immunodeficiency virus type 1 (hiv-1). however, despite the fact that interferons negatively regulate hiv-1 ex vivo, a chronic interferon state is linked to the progression of aids and to robust viral replication, rather than protection, in vivo. to explain this apparent contradiction, we hypothesized that hiv-1 may have evolved a partial re ...201323255800
rapid detection of human immunodeficiency virus types 1 and 2 by use of an improved piezoelectric biosensor.disasters can create situations in which blood donations can save lives. however, in emergency situations and when resources are depleted, on-site blood donations require the rapid and accurate detection of blood-borne pathogens, including human immunodeficiency virus types 1 and 2 (hiv-1 and hiv-2). techniques such as pcr and antibody capture by an enzyme-linked immunosorbent assay (elisa) for hiv-1 and hiv-2 are precise but time-consuming and require sophisticated equipment that is not compati ...201323515541
the efficiency of vpx-mediated samhd1 antagonism does not correlate with the potency of viral control in hiv-2-infected individuals. 201323497283
correlates of t-cell-mediated viral control and phenotype of cd8(+) t cells in hiv-2, a naturally contained human retroviral infection.while a significant proportion of hiv-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to aids and are predicted by detectable viremia. identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled. we performed a detailed study of hiv-2-specific cellular responses in a unique community cohort in guinea-bissau followed for over 2 decades ...201323558015
synthesis, structure-activity relationships, and docking studies of n-phenylarylformamide derivatives (pafas) as non-nucleoside hiv reverse transcriptase inhibitors.a series of n-phenylarylformamide derivatives (pafas) with anti-wild-type hiv-1 activity (ec(50) values) ranging from 0.3 nm to 5.1 nm and therapeutic index (ti) ranging from 10 616 to 271 000 were identified as novel non-nucleoside reverse transcriptase inhibitors. among them, compound 13g (ec(50) = 0.30 nm, ti = 184 578), 13l (ec(50) = 0.37 nm, ti = 212 819), 13m (ec(50) = 0.32 nm, ti = 260 617) and 13r (ec(50) = 0.27 nm, ti = 271 000) displayed the highest activity against this type virus nea ...201223164656
a rationally engineered anti-hiv peptide fusion inhibitor with greatly reduced immunogenicity.peptides derived from the c-terminal heptad repeat 2 (hr2) region of the hiv-1 gp41 envelope glycoprotein, so-called c peptides, are very efficient hiv-1 fusion inhibitors. we previously developed innovative gene therapeutic approaches aiming at the direct in vivo production of c peptides from genetically modified host cells and found that t cells expressing membrane-anchored or secreted c peptides are protected from hiv-1 infection. however, an unwanted immune response against such antiviral pe ...201323147734
a phenyl-thiadiazolylidene-amine derivative ejects zinc from retroviral nucleocapsid zinc fingers and inactivates hiv virions.sexual acquisition of the human immunodeficiency virus (hiv) through mucosal transmission may be prevented by using topically applied agents that block hiv transmission from one individual to another. therefore, virucidal agents that inactivate hiv virions may be used as a component in topical microbicides.201223146561
multiple platforms of a hiv-2 derived lentiviral vector for expanded utility.using the indian human immunodeficiency virus type 2 (hiv-2) isolate derived lentiviral vector (lv) system reported earlier, we have derived multiple differently configured transfer vectors. among the features imparted, the novel ones include a blue/white colony screening platform, a shorter vector backbone candidate and availability of default dual tags. simultaneously, panels with different utilities were also made using this lv. these include neomycin or puromycin or hygromycin selection mark ...201323159456
hiv-2 antiviral potency and selection of drug resistance mutations by the integrase strand transfer inhibitor elvitegravir and nrtis emtricitabine and tenofovir in vitro.hiv-2 is susceptible to only a subset of approved antiretroviral drugs. a single tablet regimen containing the integrase strand transfer inhibitor elvitegravir (evg) boosted by cobicistat plus the nucleoside reverse transcriptase (rt) inhibitors emtricitabine (ftc) and tenofovir disoproxil fumarate (evg/cobi/ftc/tdf) has potent activity against hiv-1 and may have utility against hiv-2.201323187937
resistance to antibody neutralization in hiv-2 infection occurs in late stage disease and is associated with x4 tropism.to characterize the nature and dynamics of the neutralizing antibody (nab) response and escape in chronically hiv-2 infected patients.201223151495
the carboxyl-terminus of human immunodeficiency virus type 2 circulating recombinant form 01_ab capsid protein affects sensitivity to human trim5α.human immunodeficiency virus (hiv) type 2 shows limited geographical distribution compared with hiv type 1. although 8 genetic groups of hiv type 2 (hiv-2) have been described, recombinant viruses between these groups are rarely observed. recently, three hiv-2 patients in japan were described with rapidly progressive, acquired immunodeficiency. these patients were infected with an a/b inter-group recombinant designated crf01_ab. here, we characterize the capsid protein (ca) encoded by the viruse ...201223094081
three main mutational pathways in hiv-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging hiv-2 treatment regimens.human immunodeficiency virus type 2 (hiv-2) is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors and exhibits reduced susceptibility to several of the protease inhibitors used for antiretroviral therapy of hiv-1. thus, there is a pressing need to identify new classes of antiretroviral agents that are active against hiv-2. although recent data suggest that the integrase strand transfer inhibitors raltegravir and elvitegravir may be beneficial, mutations that are known to ...201223028968
synthesis and evaluation of novel 4-substituted styryl quinazolines as potential antimicrobial agents.in an attempt to afford possible antibacterial and anti-human immunodeficiency virus (hiv) agents, a series of 22 novel styryl quinazoline-based heterocyclic entities were designed and synthesized. various substituted aryl urea and thiourea cores were incorporated at position 4 of quinazoline, followed by styrylation of position 2, aiming at an augmented biological potential. the synthesized compounds were well characterized through ir, (1) h nmr, (13) c nmr and elemental analyses. all compounds ...201223018557
hiv progression to aids: bioinformatics approach to determining the mechanism of action.the mechanism by which hiv infection transforms into aids disease is unclear. several factors such as the decline in immune response, increase in replication rate, syncytium inducing capacity and ability of the viruses to infect tumour cell lines are found to be associated with hiv progression to aids. what has not been investigated is the role of an increase in affinity for the cd4+ t cells by the hiv-1 t cell lymphocyte-loving (t-tropic) viruses. they are known to be mutants of the macrophage- ...201322998236
frequent intratype neutralization by plasma immunoglobulin a identified in hiv type 2 infection.human immunodeficiency virus type 2 (hiv-2) is less transmissible and less pathogenic compared to hiv-1 and, when matched for cd4(+) t cell count, the plasma viral load in hiv-2-infected individuals is approximately one log lower than in hiv-1-infected individuals. the explanation for these observations is elusive, but differences in virus controlling immunity generated in the two infections may be contributing factors. in the present study, we investigated neutralization by immunoglobulin a (ig ...201323088167
translation initiation is driven by different mechanisms on the hiv-1 and hiv-2 genomic rnas.the human immunodeficiency virus (hiv) unspliced full length genomic rna possesses features of an eukaryotic cellular mrna as it is capped at its 5' end and polyadenylated at its 3' extremity. this genomic rna is used both for the production of the viral structural and enzymatic proteins (gag and pol, respectively) and as genome for encapsidation in the newly formed viral particle. although both of these processes are critical for viral replication, they should be controlled in a timely manner f ...201323079111
effect of complement on hiv-2 plasma antiviral activity is intratype specific and potent.human immunodeficiency virus type 2 (hiv-2)-infected individuals develop immunodeficiency with a considerable delay and transmit the virus at rates lower than hiv-1-infected persons. conceivably, comparative studies on the immune responsiveness of hiv-1- and hiv-2-infected hosts may help to explain the differences in pathogenesis and transmission between the two types of infection. previous studies have shown that the neutralizing antibody response is more potent and broader in hiv-2 than in hiv ...201323077299
epitope mapping of broadly neutralizing hiv-2 human monoclonal antibodies.recent studies have shown that natural infection by hiv-2 leads to the elicitation of high titers of broadly neutralizing antibodies (nabs) against primary hiv-2 strains (t. i. de silva, et al., j. virol. 86:930-946, 2012; r. kong, et al., j. virol. 86:947-960, 2012; g. ozkaya sahin, et al., j. virol. 86:961-971, 2012). here, we describe the envelope (env) binding and neutralization properties of 15 anti-hiv-2 human monoclonal antibodies (mabs), 14 of which were newly generated from 9 chronicall ...201222933274
association of soluble cd14 and inflammatory biomarkers with hiv-2 disease progression.human immunodeficiency virus type 2 (hiv-2) infection is characterized by a slower progression than hiv type 1. it is not known whether markers of inflammation such as high-sensitivity c-reactive protein (hscrp), interleukin 6 (il-6), and soluble cd14 (scd14) may predict disease progression among hiv-2 patients.201222911639
samhd1-dependent and -independent functions of hiv-2/siv vpx protein.both human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) encode a unique set of accessory proteins that enhance viral replication in the host. two similar accessory proteins, vpx and vpr, are encoded by hiv-2. in contrast, hiv-1 encodes vpr but not vpx. recent studies have indicated that vpx counteracts a particular host restriction factor, thereby facilitating reverse transcription in myeloid cells such as monocyte-derived macrophages and monocyte-derived dendritic cells. ...201222908011
the role of raltegravir in the treatment of hiv-2 infections: evidence from a case series.we describe five patients with hiv-2 infection (four antiretroviral-experienced and one antiretroviral-naive) treated with a regimen containing raltegravir. all responded to treatment as demonstrated by viral load and cd4(+) t-cell count monitoring. our series confirms the clinical effectiveness of raltegravir in hiv-2-infected patients when given with other antiretrovirals to which the virus is susceptible.201222892365
[research progress of the anti-hiv activity of samhd1].the sam and hd domain containing protein 1 (sterile alpha motif domain and hd domain-containing protein 1, samhd1) is a putative negative regulator of the antiviral innate immune response. it can significantly increase the antiviral immune response, mediates the interferon-induced inflammatory response involved in the host foreign-virus defense system. the early studies have focused on its gene mutations associated with aicardi-goutières syndrome (ags), the latest study found that samhd1 as a po ...201222978176
the vpx lentiviral accessory protein targets samhd1 for degradation in the nucleus.sterile alpha motif domain- and hd domain-containing protein 1 (samhd1) is a deoxynucleoside triphosphohydrolase that restricts the replication of lentiviruses in myeloid cells by hydrolyzing the cellular deoxynucleotide triphosphates to a level below that which is required for reverse transcription. human immunodeficiency virus type 2 (hiv-2) and some simian immunodeficiency viruses (sivs) encode the accessory protein viral protein x (vpx) that counteracts samhd1. vpx recruits samhd1 to a culli ...201222973040
are plasma biomarkers of immune activation predictive of hiv progression: a longitudinal comparison and analyses in hiv-1 and hiv-2 infections?chronic immune activation is a hallmark of hiv infection and has been associated with disease progression. assessment of soluble biomarkers indicating immune activation provide clues into pathogenesis and hold promise for the development of point-of-care monitoring of hiv in resource-poor-settings. their evaluation in cohort resources is therefore needed to further their development and use in hiv research.201222970212
an analog of the natural steroidal alkaloid cortistatin a potently suppresses tat-dependent hiv transcription.the human immunodeficiency virus type 1 (hiv) tat protein, a potent activator of hiv gene expression, is essential for integrated viral genome expression and represents a potential antiviral target. tat binds the 5'-terminal region of hiv mrna's stem-bulge-loop structure, the transactivation-responsive (tar) element, to activate transcription. we find that didehydro-cortistatin a (dca), an analog of a natural steroidal alkaloid from a marine sponge, inhibits tat-mediated transactivation of the i ...201222817991
enhanced anti-hiv efficacy of indinavir after inclusion in cd4-targeted lipid nanoparticles.combination drug therapy has reduced plasma hiv to undetectable levels; however, drug-sensitive virus persists in patients' lymphoid tissue. we have reported significant lymphoid tissue drug localization with indinavir-associated lipid nanoparticles (lnps). our current objective is to evaluate whether additional enhancement is achievable by targeting these particles to cd4-hiv host cells.201222743598
synthesis, crystal structure and anti-hiv activity of 2-adamantyl/adamantylmethyl-5-aryl-1,3,4-oxadiazoles.two series of 2-adamantyl/adamantylmethyl-5-aryl-1,3,4-oxadiazoles (4a-l and 5a-l) were synthesized by cyclodehydration of adamantan-1-carboxylic acid/adamantylacetic acid with various aryl hydrazides (3a-l) in the presence of pocl(3). the synthesis was supported by spectroanalytical techniques and verified further by crystal structure determination of compounds 4e and 5k. the synthesized compounds were screened for their inhibitory activity against hiv-1 and hiv-2 in mt-4 cells. compound 5b exh ...201222741800
inhibition of hiv-1 disease progression by contemporaneous hiv-2 infection.progressive immune dysfunction and the acquired immunodeficiency syndrome (aids) develop in most persons with untreated infection with human immunodeficiency virus type 1 (hiv-1) but in only approximately 20 to 30% of persons infected with hiv type 2 (hiv-2); among persons infected with both types, the natural history of disease progression is poorly understood.201222808957
a novel dcaf1-binding motif required for vpx-mediated degradation of nuclear samhd1 and vpr-induced g2 arrest.hiv-2 and closely related siv vpx proteins are essential for viral replication in macrophages and dendritic cells. vpx hijacks dcaf1-ddb1-cul4 e3 ubiquitin ligase to promote viral replication. dcaf1 is essential for cell proliferation and embryonic development and is responsible for the polyubiquitination of poorly defined cellular proteins. how substrate receptors recruit the dcaf1-containing e3 ubiquitin ligase to induce protein degradation is still poorly understood. here we identify a highly ...201222776683
validation for clinical use of a novel hiv-2 plasma rna viral load assay using the abbott m2000 platform.optimal care of persons infected with human immunodeficiency virus type 2 (hiv-2) requires an accurate assessment of hiv-2 plasma viral load (vl), but no clinically approved quantitative hiv-2 rna vl assay exists.201222832059
enhanced u.s. army hiv diagnostic algorithm used to diagnose acute hiv infection in a deployed soldier.antibody screening alone may fail to detect human immunodeficiency virus (hiv) in recently infected individuals. by u.s. army regulation, hiv-infected soldiers are not permitted to deploy to areas of conflict, including iraq and afghanistan. we report here the first case of acute hiv infection (ahi) in a soldier in a combat area of operation detected by an enhanced u.s. army hiv testing algorithm and discuss features of the tests which aided in clinical diagnosis. we tested the sample from the a ...201222645891
[consensus document of gesida and spanish secretariat for the national plan on aids (spns) regarding combined antiretroviral treatment in adults infected by the human immunodeficiency virus (january 2012)].this consensus document has been prepared by a panel consisting of members of the aids study group (gesida) and the spanish secretariat for the national plan on aids (spns) after reviewing the efficacy and safety results of clinical trials, cohort and pharmacokinetic studies published in medical journals, or presented in medical scientific meetings. gesida has prepared an objective and structured method to prioritise combined antiretroviral treatment (cart) in naïve patients. recommendations str ...201222633764
tight interplay among samhd1 protein level, cellular dntp levels, and hiv-1 proviral dna synthesis kinetics in human primary monocyte-derived macrophages.recently, samhd1 has come under intense focus as a host anti-hiv factor. samhd1 is a dntp triphosphohydrolase, which leads to the regulation of dna metabolism in host cells. hiv-2/siv (simian immunodeficiency virus) viral protein x (vpx) has been shown to promote the degradation of samhd1. in this study, we examine the kinetics of samhd1 degradation, the increase in the dntp pool level, and the efficiency of proviral dna synthesis in vpx+ virus-like particle (vlp)-treated monocyte-derived macrop ...201222589553
vpx is critical for sivmne infection of pigtail macaques.viral protein x (vpx) of siv has been reported to be important for establishing infection in vivo. vpx has several different activities in vitro, promoting preintegration complex import into the nucleus in quiescent lymphocytes and overcoming a block in reverse transcription in macrophages. vpx interacts with the ddb1-cul4-dcaf1 e3 ligase complex, which may or may not be required for the ascribed functions. the goal of the current study was to determine whether these activities of vpx are import ...201222531456
role of human trim5α in intrinsic immunity.human immunodeficiency virus (hiv) has a very narrow host range. hiv type 1 (hiv-1) does not infect old world monkeys, such as the rhesus monkey (rh). rh trim5α was identified as a factor that confers resistance, intrinsic immunity, to hiv-1 infection. unfortunately, human trim5α is almost powerless to restrict hiv-1. however, human trim5α potently restricts n-tropic murine leukemia viruses (mlv) but not b-tropic mlv, indicating that human trim5α represents the restriction factor previously desi ...201222435067
hiv-2 genome dimerization is required for the correct processing of gag: a second-site reversion in matrix can restore both processes in dimerization-impaired mutant viruses.a unique feature of retroviruses is the packaging of two copies of their genome, noncovalently linked at their 5' ends. in vitro, dimerization of human immunodeficiency virus type 2 (hiv-2) rna occurs by interaction of a self-complementary sequence exposed in the loop of stem-loop 1 (sl-1), also termed the dimer initiation site (dis). however, in virions, hiv-2 genome dimerization does not depend on the dis. instead, a palindrome located within the packaging signal (psi) is the essential motif f ...201222419802
hiv-1 and hiv-2 infections induce autophagy in jurkat and cd4+ t cells.autophagy plays important roles during innate and adaptive immune responses to pathogens, including virus infection. viruses develop ways to subvert the pathway for their own benefit in order to escape restriction by autophagy, leading to increased viral replication and/or control over apoptosis of their host cells. the effects of hiv infection on the autophagic pathway in host cells have been little documented. using the susceptible jurkat cell line and cd4(+) t cells, we studied the relationsh ...201222406083
switching virally suppressed, treatment-experienced patients to a raltegravir-containing regimen does not alter levels of hiv-1 dna.current hiv-1 antiretroviral therapy (art) greatly reduces virus replication but does not significantly affect the viral reservoir. raltegravir, a recently introduced integrase inhibitor, could, at least theoretically, reduce residual viremia in patients on art and affect the viral reservoir size. the aim of this study was to assess whether switching therapy in treatment-experienced patients that were virally suppressed to a raltegravir-containing regimen reduces the size of the viral reservoir, ...201222396745
overview of microbicides for the prevention of human immunodeficiency virus.human immunodeficiency virus (hiv) prevention tools that women can use and control are urgently needed. microbicides are chemical products applied to the vagina or rectum to prevent the sexual transmission of hiv. four classes of candidate microbicides have been tested to date: those that (1) enhance the natural defences in the vagina to inactivate hiv; (2) inactivate hiv in the vagina; (3) prevent hiv from attaching to, and fusing with, the host cells; and (4) prevent hiv from replicating in ge ...201222386823
hiv-2 viral protein x (vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection.hiv-2 vpx, a virus-associated accessory protein, is critical for infection of non-dividing myeloid cells. to understand the function of vpx ubiquitination, interaction with an e3 ubiquitin ligase complex, and ability to overcome an inhibition of reverse transcription, we analyzed vpx lysine mutants for their function and replication capability in macrophages. both wt vpx and vpx ta (lysine-less vpx) localized to the cytoplasm and nucleus in hela cells. all hiv-2 vpx lysine mutants were functiona ...201222386056
hiv/simian immunodeficiency virus (siv) accessory virulence factor vpx loads the host cell restriction factor samhd1 onto the e3 ubiquitin ligase complex crl4dcaf1.the sterile alpha motif and hd domain-containing protein-1 (samhd1) inhibits infection of myeloid cells by human and related primate immunodeficiency viruses (hiv and siv). this potent inhibition is counteracted by the vpx accessory virulence factor of hiv-2/sivsm viruses, which targets samhd1 for proteasome-dependent degradation, by reprogramming cellular crl4(dcaf1) e3 ubiquitin ligase. however, the precise mechanism of vpx-dependent recruitment of human samhd1 onto the ligase, and the molecul ...201222362772
human immunodeficiency virus type-2-a milder, kinder virus: an update.human immunodeficiency virus type-2 (hiv-2) belongs to the family retroviridae which is phylogenetically clusters with siv sm from sooty mangabeys. this virus is morphologically similar to human immunodeficiency virus type-1 (hiv-1) but has got only a 40% homology at the nucleotide level. there is a distinct geographical distribution of hiv-2 unlike hiv-1. there are currently eight subtypes/groups identified with subtype/group a responsible for the majority of infections. hiv-2 shows a considera ...201222361754
efficient nef-mediated downmodulation of tcr-cd3 and cd28 is associated with high cd4+ t cell counts in viremic hiv-2 infection.the role of the multifunctional accessory nef protein in the immunopathogenesis of hiv-2 infection is currently poorly understood. here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load, >500 copies/ml) and 16 nonviremic (<500) hiv-2-infected individuals. on average, nef alleles from both groups were equally active in modulating cd4, tcr-cd3, cd28, mhc-i, and ii cell surface expression and in enhancing virion infectivity. thus, many hiv-2-infected ...201222345473
samhd1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates.samhd1 restricts the infection of dendritic and other myeloid cells by human immunodeficiency virus type 1 (hiv-1), but in lentiviruses of the simian immunodeficiency virus of sooty mangabey (sivsm)-hiv-2 lineage, samhd1 is counteracted by the virion-packaged accessory protein vpx. here we found that samhd1 restricted infection by hydrolyzing intracellular deoxynucleoside triphosphates (dntps), lowering their concentrations to below those required for the synthesis of the viral dna by reverse tr ...201222327569
the human immunodeficiency virus type 1 nef and vpu proteins downregulate the natural killer cell-activating ligand pvr.the human immunodeficiency virus type 1 (hiv-1) evades the immune responses of natural killer (nk) cells through mechanisms that have been partially deciphered. here we show that in hiv-1-infected t lymphocytes, the early viral nef protein downmodulates pvr (cd155, necl-5), a ligand for the activating receptor dnam-1 (cd226) expressed by all nk cells, cd8(+) t cells, and other cell types. this novel nef activity is conserved by nef proteins of laboratory hiv-1 strains (nl4-3, sf2) and of a patie ...201222301152
elicitation of neutralizing antibodies directed against cd4-induced epitope(s) using a cd4 mimetic cross-linked to a hiv-1 envelope glycoprotein.the identification of hiv-1 envelope glycoprotein (env) structures that can generate broadly neutralizing antibodies (bnabs) is pivotal to the development of a successful vaccine against hiv-1 aimed at eliciting effective humoral immune responses. to that end, the production of novel env structure(s) that might induce bnabs by presentation of conserved epitopes, which are otherwise occluded, is critical. here, we focus on a structure that stabilizes env in a conformation representative of its pr ...201222291921
trim5α and species tropism of hiv/siv.human immunodeficiency virus type 1 (hiv-1) infects humans and chimpanzees but not old world monkeys (owms) such as the rhesus monkey (rh) and cynomolgus monkey (cm). hiv-1 efficiently enters cells of owms but encounters a block before reverse transcription. this narrow host range is attributed to a barrier in the host cell. in 2004, the screening of a rh cdna library identified tripartite motif 5α (trim5α) as a cellular antiviral factor. trim5α is one of splicing variants produced by trim5 gene ...201222291694
hiv types, groups, subtypes and recombinant forms: errors in replication, selection pressure and quasispecies.hiv-1 is a chimpanzee virus which was transmitted to humans by several zoonotic events resulting in infection with hiv-1 groups m-p, and in parallel transmission events from sooty mangabey monkey viruses leading to infections with hiv-2 groups a-h. both viruses have circulated in the human population for about 80 years. in the infected patient, hiv mutates, and by elimination of some of the viruses by the action of the immune system individual quasispecies are formed. along with the selection of ...201222286874
origin of decrease in potency of darunavir and two related antiviral inhibitors against hiv-2 compared to hiv-1 protease.acquired immune deficiency syndrome (aids) is caused by the human immunodeficiency virus (hiv) type 1 and 2 (hiv-1 and hiv-2). hiv-1 is observed worldwide while hiv-2 though prevalent in west africa is persistently spreading to other parts of the world. an important target for aids treatment is the use of hiv protease (pr) inhibitors preventing the replication of the virus. in this work, the popular molecular mechanics poisson-boltzmann surface area (mm-pbsa) method has been used to investigate ...201222280246
lack of evidence of simian immunodeficiency virus infection among nonhuman primates in taï national park, côte d'ivoire: limitations of noninvasive methods and siv diagnostic tools for studies of primate retroviruses.it is now well established that the human immunodeficiency viruses, hiv-1 and hiv-2, are the results of cross-species transmissions of simian immunodeficiency viruses (siv) naturally infecting nonhuman primates in sub-saharan africa. sivs are found in many african primates, and humans continue to be exposed to these viruses by hunting and handling primate bushmeat. sooty mangabeys (cercocebus atys) and western red colobus (piliocolobus badius badius) are infected with siv at a high rate in the t ...201123950618
[rheumatic disorders observed in hiv infected patients undergoing highly active antiretroviral therapy (haart): a 366 case prospective study in burkina faso].the purpose of this report is to describe epidemiological aspects of rheumatic disorders observed in hiv-infected patients undergoing highly active antiretroviral therapy (haart). patients and methods. this cross-sectional study was conducted from january 1 to june 30, 2008 in the hiv unit of an internal medicine department in burkina faso. all patients who had been undergoing haart for at least one year were included. interviewing and thorough physical examination were performed in all cases. r ...201022368930
genomic diversity of human immunodeficiency viruses.globally circulating strains of human immunodeficiency virus type one (hiv-1) exhibit an extraordinary degree of genetic diversity. sequences derived from hiv-1 strains have historically been classified on the basis of their phylogenetic relationships. the viruses have been classified into groups, subtypes or clades and circulating recombinant forms (crfs). groups were originally named m for main, o for outlier and n for non-m-non-o. the identification of subtypes and crfs provides a means of tr ...200527407775
performance evaluation of a new fourth-generation hiv combination antigen-antibody assay.education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (hiv). the importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. the elecsys(®) hiv combi pt assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and impro ...201322706797
electrostatic potential of human immunodeficiency virus type 2 and rhesus macaque simian immunodeficiency virus capsid proteins.human immunodeficiency virus type 2 (hiv-2) and simian immunodeficiency virus isolated from a macaque monkey (sivmac) are assumed to have originated from simian immunodeficiency virus isolated from sooty mangabey (sivsm). despite their close similarity in genome structure, hiv-2 and sivmac show different sensitivities to trim5α, a host restriction factor against retroviruses. the replication of hiv-2 strains is potently restricted by rhesus (rh) monkey trim5α, while that of sivmac strain 239 (si ...201222679444
apobec3f constitutes a barrier to successful cross-species transmission of simian immunodeficiency virus sivsmm to humans.simian immunodeficiency virus infecting sooty mangabeys (sivsmm) has been transmitted to humans on at least nine occasions, giving rise to human immunodeficiency virus type 2 (hiv-2) groups a to i. sivsmm isolates replicate in human t cells and seem capable of overcoming major human restriction factors without adaptation. however, only groups a and b are responsible for the hiv-2 epidemic in sub-saharan africa, and it is largely unclear whether adaptive changes were associated with spread in hum ...202134132575
interplay between hiv-1 and host genetic variation: a snapshot into its impact on aids and therapy response.as of february 2012, 50 circulating recombinant forms (crfs) have been reported for hiv-1 while one crf for hiv-2. also according to hiv sequence compendium 2011, the hiv sequence database is replete with 414,398 sequences. the fact that there are crfs, which are an amalgamation of sequences derived from six or more subtypes (crf27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent e ...201222666249
increased gonorrhea cases - utah, 2009-2014.gonorrhea (caused by infection with neisseria gonorrhoeae) is the second most commonly reported notifiable disease in the united states (1). left untreated, gonorrhea is associated with serious long-term adverse health effects, including pelvic inflammatory disease, ectopic pregnancy, and infertility. infection also facilitates transmission of human immunodeficiency virus (2,3). effective gonorrhea control relies upon early detection and effective antimicrobial treatment. to assess gonorrhea rat ...201627583786
hiv-2:the implications.in 1983, the aetiological agent of aids was discovered by french scientists and was termed the 'lym- phadenopathy-associated virus' (lav) [ 1 ]. a year later, american researchers also described this retrovirus and termed it the 'human t-cell leukemia virus, type iii' (htlv-iii) [ 2 ], both lav and htlv-iii were the same retrovirus and in 1986, it was agreed that the viruses which can cause aids be termed the 'human immunodeficiency viruses' (hiv).198827223918
Displaying items 2601 - 2683 of 2683