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characterization of the interactions between sivrcm vpx and red-capped mangabey samhd1.samhd1 (sam domain- and hd domain-containing protein 1) inhibits hiv-1 infection of myeloid cells and resting cd4+ t-cells. two lineages of primate lentiviruses, the sooty mangabey siv (simian immunodeficiency virus) (sivsm)/macaque siv (sivmac)/hiv-2 lineage and the red-capped mangabey siv (sivrcm) lineage, carry a samhd1 antagonist called vpx. vpx recognizes samhd1 and recruits a ubiquitin e3 ligase complex that is composed of cul4 (cullin4), ddb1 (damaged dna-binding protein 1) and a member o ...201525791246
laboratory-confirmed hiv and sexually transmitted infection seropositivity and risk behavior among sexually active transgender patients at an adolescent and young adult urban community health center.the sexual health of transgender adolescents and young adults who present for health care in urban community health centers is understudied. a retrospective review of electronic health record (ehr) data was conducted from 180 transgender patients aged 12-29 years seen for one or more health-care visits between 2001 and 2010 at an urban community health center serving youth in boston, ma. analyses were restricted to 145 sexually active transgender youth (87.3% of the sample). laboratory-confirmed ...201525790139
degradation of samhd1 by vpx is independent of uncoating.sterile alpha motif domain and hd domain-containing protein 1 (samhd1) restricts human immunodeficiency virus type 1 (hiv-1) replication in myeloid and resting t cells. lentiviruses such as hiv-2 and some simian immunodeficiency viruses (sivs) counteract the restriction by encoding vpx or vpr, accessory proteins that are packaged in virions and which, upon entry of the virus into the cytoplasm, induce the proteasomal degradation of samhd1. as a tool to study these mechanisms, we generated hela c ...201525762741
aav-expressed ecd4-ig provides durable protection from multiple shiv challenges.long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for hiv-1. adeno-associated virus (aav) vectors can stably express hiv-1 broadly neutralizing antibodies (bnabs). however, even the best bnabs neutralize 10-50% of hiv-1 isolates inefficiently (80% inhibitory concentration (ic80) > 5 μg ml(-1)), suggesting that high concentrations of these antibodies would be necessary to achieve general protection. here we show that ecd4-ig, a ...201525707797
dolutegravir in hiv-2-infected patients with resistant virus to first-line integrase inhibitors from the french named patient program.dolutegravir has shown in vitro activity against human immunodeficiency virus type 2 (hiv-2). we report safety and efficacy data of regimens containing dolutegravir (50 mg twice daily) in antiretroviral-experienced, hiv-2-infected patients.201525690598
hiv-2 infects resting cd4+ t cells but not monocyte-derived dendritic cells.human immunodeficiency virus-type 2 (hiv-2) encodes vpx that degrades samhd1, a cellular restriction factor active in non-dividing cells. hiv-2 replicates in lymphocytes but the susceptibility of monocyte-derived dendritic cells (mddcs) to in vitro infection remains partly characterized.201525582927
hiv-induced epigenetic alterations in host cells.human immunodeficiency virus (hiv), a member of the retroviridae family, is a positive-sense, enveloped rna virus. hiv, the causative agent of acquired immunodeficiency syndrome (aids) has two major types, hiv-1 and hiv-2 in hiv-infected cells the single stranded viral rna genome is reverse transcribed and the double-stranded viral dna integrates into the cellular dna, forming a provirus. the proviral hiv genome is controlled by the host epigenetic regulatory machinery. cellular epigenetic regul ...201626659262
the performance of reverse transcriptase assay for the estimation of the plasma viral load in hiv-1 and hiv-2 infections.viral load testing for human immunodeficiency virus 1 (hiv-1) in resource-poor settings continues to be a challenge. although antiretroviral therapy (art) is being made available in developing countries, monitoring of viral load is not being done on a regular basis. the purpose of this study was to assess the utility of cavidi version 3.0, which measures the plasma reverse transcriptase (rt) activity and compare its performance with molecular hiv viral load assays. in all, 125 hiv-1 and 13 hiv-2 ...201626654354
phylogenetic insights into the functional relationship between primate lentiviral reverse transcriptase and accessory proteins vpx/vpr.the efficiency of reverse transcription to synthesize viral dna in infected cells greatly influences replication kinetics of retroviruses. however, viral replication in non-dividing cells such as resting t cells and terminally differentiated macrophages is potently and kinetically restricted by a host antiviral factor designated samhd1 (sterile alpha motif and hd-domain containing protein 1). samhd1 reduces cellular deoxynucleoside triphosphate (dntp) pools and affects viral reverse transcriptio ...201627803699
vif proteins from diverse human immunodeficiency virus/simian immunodeficiency virus lineages have distinct binding sites in a3c.lentiviruses have evolved the vif protein to counteract apobec3 (a3) restriction factors by targeting them for proteasomal degradation. previous studies have identified important residues in the interface of human immunodeficiency virus type 1 (hiv-1) vif and human apobec3c (ha3c) or human apobec3f (ha3f). however, the interaction between primate a3c proteins and hiv-1 vif or natural hiv-1 vif variants is still poorly understood. here, we report that hiv-1 vif is inactive against a3cs of rhesus ...201627581978
lineage-specific differences between the gp120 inner domain layer 3 of human immunodeficiency virus and that of simian immunodeficiency virus.binding of human immunodeficiency virus type 1 (hiv-1) and simian immunodeficiency virus (siv) gp120 exterior envelope glycoprotein to cd4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually ccr5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. we previously described that topological layers (layer 1, layer 2, and layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded sta ...201627535053
samhd1 polymorphisms were significantly correlated with hiv/siv virus load in pbmc from chinese rhesus macaques and cynomolgus macaquesbackground-sterile alpha motif and histidine aspartate domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (samhd1) is one of the novel restriction factors that potently supresses hiv-1 infection in myeloid cells at an early stage in the viral replication cycle. samhd1 activity is blocked by the action of viral accessory protein x (vpx), which targets and recruits samhd1 for proteasomal degradation, in the sivsm/hiv-2 lineage. objective-the impact of samhd1 polymorphisms on vira ...201627758709
single amino acid substitution n659d in hiv-2 envelope glycoprotein (env) impairs viral release and hampers bst-2 antagonism.bst-2 or tetherin is a host cell restriction factor that prevents the budding of enveloped viruses at the cell surface, thus impairing the viral spread. several countermeasures to evade this antiviral factor have been positively selected in retroviruses: the human immunodeficiency virus type 2 (hiv-2) relies on the envelope glycoprotein (env) to overcome bst-2 restriction. the env gp36 ectodomain seems involved in this anti-tetherin activity, however residues and regions interacting with bst-2 a ...201627754450
antagonism of bst-2/tetherin is a conserved function of the env glycoprotein of primary hiv-2 isolates.although hiv-2 does not encode a vpu gene, the ability to antagonize bone marrow stromal antigen 2 (bst-2) is conserved in some hiv-2 isolates, where it is controlled by the env glycoprotein. we previously reported that a single-amino-acid difference between the laboratory-adapted rod10 and rod14 envs controlled the enhancement of virus release (referred to here as vpu-like) activity. here, we investigated how conserved the vpu-like activity is in primary hiv-2 isolates. we found that half of th ...201627681141
targeted isolation of antibodies directed against major sites of siv env vulnerability.the simian immunodeficiency virus (siv) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (hiv-1) for studying vaccine mediated and immune correlates of protection. however, knowledge of the structure of the siv envelope (env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of siv antibody responses. in this study we describe the use of a competitive probe binding sort strategy as well as scaff ...201627064278
samhd1 in retroviral restriction and innate immune sensing--should we leash the hound?the antiviral restriction factor sam domain and hd domain-containing protein 1 (samhd1) is a dntp triphosphohydrolase and thereby contributes to the regulation of intracellular dntp levels. samhd1 blocks retroviral infection at the level of reverse transcription in myeloid cells and resting cd4+ t cells and is counteracted by the accessory protein vpx, which is encoded by human immunodeficiency virus 2 (hiv-2) and several simian immunodeficiency virus (siv) strains. recently, it has been shown t ...201626957197
samhd1 transcript upregulation during siv infection of the central nervous system does not associate with reduced viral load.restriction of hiv-1 in myeloid-lineage cells is attributed in part to the nucleotidase activity of the sam-domain and hd-domain containing protein (samhd1), which depletes free nucleotides, blocking reverse transcription. in the same cells, the vpx protein of hiv-2 and most sivs counteracts samhd1. both type i and ii interferons may stimulate samhd1 transcription. the contributions of samhd1 to retroviral restriction in the central nervous system (cns) have been the subject of limited study. we ...201626936683
infant deaths due to herpes simplex virus, congenital syphilis, and hiv in new york city.neonatal infection with herpes simplex virus (hsv) is not a nationally reportable disease; there have been few population-based measures of hsv-related infant mortality. we describe infant death rates due to neonatal hsv as compared with congenital syphilis (cs) and hiv, 2 reportable, perinatally transmitted diseases, in new york city from 1981 to 2013.201626933212
metabolic profiling during hiv-1 and hiv-2 infection of primary human monocyte-derived macrophages.we evaluated cellular metabolism profiles of hiv-1 and hiv-2 infected primary human monocyte-derived macrophages (mdms). first, hiv-2 gl-an displays faster production kinetics and greater amounts of virus as compared to hiv-1s: yu-2, 89.6 and jr-csf. second, quantitative lc-ms/ms metabolomics analysis demonstrates very similar metabolic profiles in glycolysis and tca cycle metabolic intermediates between hiv-1 and hiv-2 infected macrophages, with a few notable exceptions. the most striking metab ...201626895248
high-frequency illegitimate strand transfers of nascent dna fragments during reverse transcription result in defective retrovirus genomes.two strand transfers of nascent dna fragments during reverse transcription are required for retrovirus replication. however, whether strand transfers occur at illegitimate sites and how this may affect retrovirus replication are not well understood.201626885810
potent in vitro antiviral activity of cistus incanus extract against hiv and filoviruses targets viral envelope proteins.novel therapeutic options are urgently needed to improve global treatment of virus infections. herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. here we demonstrate that cistus incanus (ci) herbal products inhibit human immunodeficiency virus (hiv) infections in vitro. ci extract inhibited clinical hiv-1 and hiv-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad ...201626833261
analysis of host gene expression profile in hiv-1 and hiv-2 infected t-cells.hiv replication is closely regulated by a complex pathway of host factors, many of them being determinants of cell tropism and host susceptibility to hiv infection. these host factors are known to exert a positive or negative influence on the replication of the two major types of hiv, hiv-1 and hiv-2, thereby modulating virus infectivity, host response to infection and ultimately disease progression profiles characteristic of these two types. understanding the differential regulation of host cel ...201626821323
the cellular thioredoxin-1/thioredoxin reductase-1 driven oxidoreduction represents a chemotherapeutic target for hiv-1 entry inhibition.the entry of hiv into its host cell is an interesting target for chemotherapeutic intervention in the life-cycle of the virus. during entry, reduction of disulfide bridges in the viral envelope glycoprotein gp120 by cellular oxidoreductases is crucial. the cellular thioredoxin reductase-1 plays an important role in this oxidoreduction process by recycling electrons to thioredoxin-1. therefore, thioredoxin reductase-1 inhibitors may inhibit gp120 reduction during hiv-1 entry. in this present stud ...201626816344
acute infections, cost per infection and turnaround time in three united states hospital laboratories using fourth-generation antigen-antibody human immunodeficiency virus immunoassays.background.  to improve clinical and public health outcomes through early human immunodeficiency virus (hiv) detection, fourth-generation antigen/antibody immunoassay (4ia) and supplemental testing results must be returned rapidly. methods.  we examined hiv testing data at harborview medical center (hmc), massachusetts general hospital (mgh), and the medical university of south carolina (musc), which used 4ia and supplemental antibody and nucleic acid tests (nats). at mgh and musc, hiv-1 western ...201626798766
hd domain of samhd1 influences vpx-induced degradation at a post-interaction step.primate samhd1 proteins are potent inhibitors of viruses, including retroviruses such as hiv-1, hiv-2, and siv. vpx, a distinctive viral protein expressed by hiv-2 and some sivs, induces samhd1 degradation by forming a vpx-dcaf1-based ubiquitin ligase complex. either the n- or the c-terminus of samhd1 is critical for vpx-induced degradation, depending on the types of samhd1 and vpx proteins. however, it was not fully understood whether other regions of samhd1 also contribute to its depletion by ...201626779819
a pan-hiv strategy for complete genome sequencing.molecular surveillance is essential to monitor hiv diversity and track emerging strains. we have developed a universal library preparation method (hiv-smart [i.e.,switchingmechanismat 5' end ofrnatranscript]) for next-generation sequencing that harnesses the specificity of hiv-directed priming to enable full genome characterization of all hiv-1 groups (m, n, o, and p) and hiv-2. broad application of the hiv-smart approach was demonstrated using a panel of diverse cell-cultured virus isolates. hi ...201626699702
human milk banking.human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. the largest group of recipients are premature infants who derive very substantial benefits from it. human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. milk banks collect, screen, store, process, and distribute human milk. donating women usually nurse their own infants and have a milk supply that ex ...201628103607
a genotypic method for determining hiv-2 coreceptor usage enables epidemiological studies and clinical decision support.ccr5-coreceptor antagonists can be used for treating hiv-2 infected individuals. before initiating treatment with coreceptor antagonists, viral coreceptor usage should be determined to ensure that the virus can use only the ccr5 coreceptor (r5) and cannot evade the drug by using the cxcr4 coreceptor (x4-capable). however, until now, no online tool for the genotypic identification of hiv-2 coreceptor usage had been available. furthermore, there is a lack of knowledge on the determinants of hiv-2 ...201627998283
tlr7/8 agonist induces a post-entry samhd1-independent block to hiv-1 infection of monocytes.monocytes, the primary myeloid cell-type in peripheral blood, are resistant to hiv-1 infection as a result of the lentiviral restriction factor samhd1. toll-like receptors recognize microbial pathogen components, inducing the expression of antiviral host proteins and proinflammatory cytokines. tlr agonists that mimic microbial ligands have been found to have activity against hiv-1 in macrophages. the induction of restriction factors in monocytes by tlr agonist activation has not been well studie ...201627905985
early diagnosis of hiv infection in infants - one caribbean and six sub-saharan african countries, 2011-2015.pediatric human immunodeficiency virus (hiv) infection remains an important public health issue in resource-limited settings. in 2015, 1.4 million children aged <15 years were estimated to be living with hiv (including 170,000 infants born in 2015), with the vast majority living in sub-saharan africa (1). in 2014, 150,000 children died from hiv-related causes worldwide (2). access to timely hiv diagnosis and treatment for hiv-infected infants reduces hiv-associated mortality, which is approximat ...201627880749
preservation of lymphopoietic potential and virus suppressive capacity by cd8+ t cells in hiv-2-infected controllers.compared with hiv-1, hiv-2 infection is characterized by a larger proportion of slow or nonprogressors. a better understanding of hiv-2 pathogenesis should open new therapeutic avenues to establish control of hiv-1 replication in infected patients. in this study, we studied the production of cd8(+) t cells and their capacity for viral control in hiv-2 controllers from the french anrs co5 hiv-2 cohort. hiv-2 controllers display a robust capacity to support long-term renewal of the cd8(+) t cell c ...201627566819
expression profiles of vpx/vpr proteins are co-related with the primate lentiviral lineage.viruses of human immunodeficiency virus type 2 (hiv-2) and some simian immunodeficiency virus (siv) lineages carry a unique accessory protein called vpx. vpx is essential or critical for viral replication in natural target cells such as macrophages and t lymphocytes. we have previously shown that a poly-proline motif (ppm) located at the c-terminal region of vpx is required for its efficient expression in two strains of hiv-2 and sivmac, and that the vpx expression levels of the two clones are s ...201627536295
hiv-2 molecular epidemiology.the simian immunodeficiency virus of sooty mangabeys (sivsmm) has been revealed to be at the origin of human immunodeficiency virus type 2 (hiv-2) in humans, firstly detected from two portuguese patients in 1986. hiv-2 is mainly restricted to west africa where it infects up to 1 to 2 million people. hiv-2 is also present in europe, mainly portugal and france, india and united states of america. two major hiv-2 groups, groups a and b, were generated by two independent transmission events involvin ...201627530215
access of hiv-2 to cd169-dependent dendritic cell-mediated trans infection pathway is attenuated.the mechanisms behind the low viral loads and lower mortality rates of hiv-2(+) individuals remain unknown. we hypothesized that reduced interaction of hiv-2 with cd169, the primary hiv-1 attachment factor on monocyte-derived dendritic cells (dcs) that targets captured virus particles to the trans infection pathway, contributes to its diminished pathogenic phenotype in vivo. we observed a significant decrease in capture of hiv-2 gag-egfp virus-like particles (vlps) and infectious gfp-containing ...201627521724
diagnostic utility of droplet digital pcr for hiv reservoir quantification.quantitative real-time pcr (qpcr) is implemented in many molecular laboratories worldwide for the quantification of viral nucleic acids. however, over the last two decades, there has been renewed interest in the concept of digital pcr (dpcr) as this platform offers direct quantification without the need for standard curves, a simplified workflow and the possibility to extend the current detection limit. these benefits are of great interest in terms of the quantification of low viral levels in hi ...201627482456
human immunodeficiency virus type 2 (hiv-2) gag is trafficked in an ap-3 and ap-5 dependent manner.although human immunodeficiency virus (hiv) types 1 and 2 are closely related lentiviruses with similar replication cycles, hiv-2 infection is associated with slower progression to aids, a higher proportion of long term non-progressors, and lower rates of transmission than hiv-1, likely as a consequence of a lower viral load during hiv-2 infection. a mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between hiv-1 and hiv-2 ...201627392064
h11/hspb8 restricts hiv-2 vpx to restore the anti-viral activity of samhd1.virus-host interactions play vital roles in viral replication and virus-induced pathogenesis. viruses rely entirely upon host cells to reproduce progeny viruses; however, host factors positively or negatively regulate virus replication by interacting with viral proteins. the elucidation of virus-host protein interaction not only provides a better understanding of the molecular mechanisms by which host cells combat viral infections, but also facilitates the development of new anti-viral therapeut ...201627379031
hiv-1 and hiv-2 exhibit divergent interactions with hltf and ung2 dna repair proteins.hiv replication in nondividing host cells occurs in the presence of high concentrations of noncanonical dutp, apolipoprotein b mrna-editing, enzyme-catalytic, polypeptide-like 3 (apobec3) cytidine deaminases, and samhd1 (a cell cycle-regulated dntp triphosphohydrolase) dntpase, which maintains low concentrations of canonical dntps in these cells. these conditions favor the introduction of marks of dna damage into viral cdna, and thereby prime it for processing by dna repair enzymes. accessory pr ...201627335459
dual simian foamy virus/human immunodeficiency virus type 1 infections in persons from côte d'ivoire.zoonotic transmission of simian retroviruses in west-central africa occurring in primate hunters has resulted in pandemic spread of human immunodeficiency viruses (hivs) and human t-lymphotropic viruses (htlvs). while simian foamy virus (sfv) and simian t- lymphotropic virus (stlv)-like infection were reported in healthy persons exposed to nonhuman primates (nhps) in west-central africa, less is known about the distribution of these viruses in western africa and in hospitalized populations. we s ...201627310836
nonhuman primate ifitm proteins are potent inhibitors of hiv and siv.interferon-induced transmembrane (ifitm) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including hiv. here we report cloning and characterization of a panel of nonhuman primate ifitms. we show that, similar to human ifitm, nonhuman primate ifitm proteins inhibit hiv and other primate lentiviruses. while some nonhuman primate ifitm proteins are more potent than human counterparts to inhibit hiv-1, they are generally not effective against hiv-2 si ...201627257969
normal pressure hydrocephalus in a human immunodeficiency virus type 1 patient.normal pressure hydrocephalus (nph) is a relatively common disease of adulthood characterized by a typical combination of clinical and radiological findings. in this report, we discuss a 54-year-old female presenting with symptoms suggestive of nph and found to have a history of human immunodeficiency virus (hiv) type 1. she was not treated as she was in denial state and developed nph as a possible complication. in the literature, there has only been one reported case of hiv type 2 causing nph; ...201627222676
functional incompatibility between the generic nf-κb motif and a subtype-specific sp1iii element drives the formation of the hiv-1 subtype c viral promoter.of the various genetic subtypes of human immunodeficiency virus types 1 and 2 (hiv-1 and hiv-2) and simian immunodeficiency virus (siv), only in subtype c of hiv-1 is a genetically variant nf-κb binding site found at the core of the viral promoter in association with a subtype-specific sp1iii motif. how the subtype-associated variations in the core transcription factor binding sites (tfbs) influence gene expression from the viral promoter has not been examined previously. using panels of infecti ...201627194770
hiv-1 vpu mediates hla-c downregulation.many pathogens evade cytotoxic t lymphocytes (ctls) by downregulating hla molecules on infected cells, but the loss of hla can trigger nk cell-mediated lysis. hiv-1 is thought to subvert ctls while preserving nk cell inhibition by nef-mediated downregulation of hla-a and -b but not hla-c molecules. we find that hla-c is downregulated by most primary hiv-1 clones, including transmitted founder viruses, in contrast to the laboratory-adapted nl4-3 virus. hla-c reduction is mediated by viral vpu and ...201627173934
identification of host micro rnas that differentiate hiv-1 and hiv-2 infection using genome expression profiling techniques.while human immunodeficiency virus type 1 and 2 (hiv-1 and hiv-2) share many similar traits, major differences in pathogenesis and clinical outcomes exist between the two viruses. the differential expression of host factors like micrornas (mirnas) in response to hiv-1 and hiv-2 infections are thought to influence the clinical outcomes presented by the two viruses. micrornas are small non-coding rna molecules which function in transcriptional and post-transcriptional regulation of gene expression ...201627144577
development of an antigen-capture elisa for the detection of the p27-ca protein of herv-k(hml-2).the detection or quantification of retroviruses is often achieved using an antigen-capture elisa (ac-elisa) that targets the gag capsid (ca) protein. we report here the development of an ac-elisa specific for the p27-ca protein of herv-k(hml-2). a monoclonal p27-specific antibody is used for capture and a polyclonal anti-p27-ca immune serum generated in rabbits serves for detection. the assay was shown to be specific for herv-k(hml-2), showing no evidence of cross reactivity with the human retro ...201627142113
two human immunodeficiency virus type 2 cases in us blood donors including serologic, molecular, and genomic characterization of an epidemiologically unusual case.blood donation screening for human immunodeficiency virus type 2 (hiv-2) has been in place in the united states since 1992. however, only three hiv-2 antibody-positive donors have been reported to date, all detected via hiv-1 cross-reactivity.201627079968
sun2 overexpression deforms nuclear shape and inhibits hiv.in a previous screen of putative interferon-stimulated genes, sun2 was shown to inhibit hiv-1 infection in an uncharacterized manner. sun2 is an inner nuclear membrane protein belonging to the linker of nucleoskeleton and cytoskeleton complex. we have analyzed here the role of sun2 in hiv infection. we report that in contrast to what was initially thought, sun2 is not induced by type i interferon, and that sun2 silencing does not modulate hiv infection. however, sun2 overexpression in cell lines ...201626865710
qualitative real-time pcr assay for hiv-1 and hiv-2 rna.because western blotting occasionally causes cross-reactions between human immunodeficiency virus (hiv)-1 and hiv-2, it is difficult to distinguish a coinfection status from a false-positive result. therefore, we developed a qualitative real-time pcr assay to detect hiv-1 and hiv-2 rna that can be performed in parallel. viral rna extracted from 500 μl of plasma was examined using real-time pcr with minor groove binder probes. bovine leukemia virus was used as an internal standard. the sensitivit ...201626743143
determinants of fiv and hiv vif sensitivity of feline apobec3 restriction factors.feline immunodeficiency virus (fiv) is a global pathogen of felidae species and a model system for human immunodeficiency virus (hiv)-induced aids. in felids such as the domestic cat (felis catus), apobec3 (a3) genes encode for single-domain a3z2s, a3z3 and double-domain a3z2z3 anti-viral cytidine deaminases. the feline a3z2z3 is expressed following read-through transcription and alternative splicing, introducing a previously untranslated exon in frame, encoding a domain insertion called linker. ...201627368163
a machine learning approach for microrna precursor prediction in retro-transcribing virus genomes.identification of microrna (mirna) precursors has seen increased efforts in recent years. the difficulty in experimental detection of pre-mirnas increased the usage of computational approaches. most of these approaches rely on machine learning especially classification. in order to achieve successful classification, many parameters need to be considered such as data quality, choice of classifier settings, and feature selection. for the latter one, we developed a distributed genetic algorithm on ...201628187417
increased hepatitis c virus (hcv) detection in women of childbearing age and potential risk for vertical transmission - united states and kentucky, 2011-2014.hepatitis c virus (hcv) infection is a leading cause of liver-related morbidity and mortality (1). transmission of hcv is primarily via parenteral blood exposure, and hcv can be transmitted vertically from mother to child. vertical transmission occurs in 5.8% (95% confidence interval = 4.2%-7.8%) of infants born to women who are infected only with hcv and in up to twice as many infants born to women who are also infected with human immunodeficiency virus (hiv) (2) or who have high hcv viral load ...201627442053
six-week follow-up after hiv-1 exposure: a position statement from the public health agency of sweden and the swedish reference group for antiviral therapy.in 2014 the public health agency of sweden and the swedish reference group for antiviral therapy (rav) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (hiv). up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, cou ...201626414596
buccal cancer in a female patient with human immunodeficiency virus-2 infection.this is the first-case report of isolated human immunodeficiency virus-2 (hiv-2) infection that developed squamous cell carcinoma (scc) of the buccal mucosa. she was treated with radiotherapy 66 gy in 30 fractions. hiv-2 infection was diagnosed with tridot test, and quantitative estimation was done with polymerase chain reaction. viral load is usually low in hiv-2 patients; similarly tempo of disease progression is also slow. treatment of scc of buccal mucosa with or without hiv infection is not ...201626458687
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
screening for human immunodeficiency virus, hepatitis b virus, hepatitis c virus, and treponema pallidum by blood testing using a bio-flash technology-based algorithm before gastrointestinal endoscopy.currently, conventional enzyme immunoassays which use manual gold immunoassays and colloidal tests (gicts) are used as screening tools to detect treponema pallidum (syphilis), hepatitis b virus (hbv), hepatitis c virus (hcv), human immunodeficiency virus type 1 (hiv-1), and hiv-2 in patients undergoing surgery. the present observational, cross-sectional study compared the sensitivity, specificity, and work flow characteristics of the conventional algorithm with manual gicts with those of a newly ...201627707942
evaluation of the procleix ultrio elite assay and the panther-system for individual nat screening of blood, hematopoietic stem cell, tissue and organ donors.the performance of the multiplex procleix ultrio elite assay as individual donor nucleic acid test (id-nat) for the detection of hiv-1, hiv-2, hcv, and hbv was evaluated in a retrospective, single center study.201627403089
origin and diversity of human retroviruses.simian immunodeficiency viruses, simian t‑cell lymphotropic viruses, and simian foamy viruses from nonhuman primates have crossed the species barrier to humans at several time points, leading to the hiv and human t lymphotropic virus epidemic and to sporadic cases of human infections with simian foamy viruses, respectively. efficient infection and spread in humans differs between simian foamy virus, simian lymphotropic virus, and simian immunodeficiency virus, but seems also to differ among the ...201724584106
facile functionalization at the c4 position of pyrimidine nucleosides via amide group activation with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (bop) and biological evaluations of the products.reactions of o-t-butyldimethylsilyl-protected thymidine, 2'-deoxyuridine, and 3'-azidothymidine (azt) with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (bop) leads to activation of the c4 amide carbonyl by formation of putative o(4)-(benzotriazol-1-yl) derivatives. subsequent substitution with alkyl and aryl amines, thiols, and alcohols leads to facile functionalization at this position. reactions with amines and thiols were conducted either as a two-step, one-pot tra ...201728054092
influence of vitamin d on liver fibrosis in chronic hepatitis c: a systematic review and meta-analysis of the pooled clinical trials data.to investigate the relationship between vitamin d and liver fibrosis in hepatitis c-monoinfected or hepatitis c virus (hcv)-human immunodeficiency virus (hiv) co-infected patients.201728261385
phylogeographical analysis reveals distinct sources of hiv-1 and hcv transmitted to former blood donors in china.historically, coinfection of hiv and hepatitis c virus (hcv) was frequent among chinese former blood donors (fbds). this is largely due to ignorance/lack of education regarding appropriate sterilizing techniques and/or the availability of single-use needles and equipment. although hcv shares identical transmission routes with hiv, the source of hcv in the chinese blood donor population still remains unknown. in this study, we investigated the evolution and transmission of hcv and hiv in the chin ...201727473534
a comprehensive serological and supplemental evaluation of hepatitis b "seroyield" blood donors: a cross-sectional study from a tertiary healthcare center in india.the present study addressed the interesting findings of supplemental evaluation of hepatitis b "seroyield" donors.201726420943
the small-molecule 3g11 inhibits hiv-1 reverse transcription.the small-molecule 6-(tert-butyl)-4-phenyl-4-(trifluoromethyl)-1h,3h-1,3,5-triazin-2-one (3g11) inhibits hiv-1 replication in the human t cell line mt-2. here, we showed that 3g11 specifically and potently blocks hiv-1 infection. by contrast, 3g11 did not block other retroviruses such as hiv-2, simian immunodeficiency virus (sivmac ), bovine immunodeficiency virus, feline immunodeficiency virus, equine infectious anemia virus, n-tropic murine leukemia virus, b-tropic murine leukemia virus, and m ...201727748043
executive summary of the gesida/national aids plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated january 2016).in this update, antiretroviral therapy (art) is recommended for all patients infected by type 1 human immunodeficiency virus (hiv-1). the objective of art is to achieve an undetectable plasma viral load (pvl). initial art should comprise 3 drugs, namely, 2 nucleoside reverse transcriptase inhibitors (nrti), and 1 drug from another family. four of the recommended regimens, all of which have an integrase strand transfer inhibitor (insti) as the third drug, are considered a preferred regimen; a fur ...201727068257
current status of hiv/aids in the art era.human immunodeficiency virus (hiv) spread to humans from chimpanzees (hiv-1 groups m and n), gorillas (hiv-1 groups p and o), and sooty mangabeys (hiv-2). hiv is spread mainly through blood or body fluids. subjects can become infected with hiv by sexual contact, needle sharing, blood transfusions, or maternal transmissions as a blood-borne virus or via breast-milk. the incubation period of hiv-1 from infection to the development of aids ranges from 8 to 11 years. in the past 3 decades, hiv has c ...201727825722
physiological mg(2+) conditions significantly alter the inhibition of hiv-1 and hiv-2 reverse transcriptases by nucleoside and non-nucleoside inhibitors in vitro.reverse transcriptases (rts) are typically assayed in vitro with 5-10 mm mg(2+), whereas the free mg(2+) concentration in cells is much lower. artificially high mg(2+) concentrations used in vitro can misrepresent different properties of human immunodeficiency virus (hiv) rt, including fidelity, catalysis, pausing, and rnase h activity. here, we analyzed nucleoside (nrtis) and non-nucleoside rt inhibitors (nnrtis) in primer extension assays at different concentrations of free mg(2+). at low conc ...201727936595
zinc binding site of hiv-2 vpx prevents instability and dysfunction of the protein.hiv-2 vpx coordinates zinc through residues h39, h82, c87 and c89. we reported previously that h39, h82 and c87 mutants maintain vpx activity to facilitate the degradation of samhd1. herein, the expression of vpx mutants in cells was examined in detail. we demonstrated that the zinc-binding site stabilizes the protein to keep its function in virus growth when low levels of vpx are expressed. at higher levels of expression, vpx aggregation can occur, and zinc binding would suppress such aggregati ...201728056217
proteolysis of mature hiv-1 p6 gag protein by the insulin-degrading enzyme (ide) regulates virus replication in an env-dependent manner.there is a significantly higher risk for type ii diabetes in hiv-1 carriers, albeit the molecular mechanism for this hiv-related pathology remains enigmatic. the 52 amino acid hiv-1 p6 gag protein is synthesized as the c-terminal part of the gag polyprotein pr55. in this context, p6 promotes virus release by its two late (l-) domains, and facilitates the incorporation of the viral accessory protein vpr. however, the function of p6 in its mature form, after proteolytic release from gag, has not b ...201728388673
the hiv oligonucleotide database (hivoligodb).the human immunodeficiency virus (hiv) is associated with one of the most widespread infectious disease, the acquired immunodeficiency syndrome (aids). the development of antiretroviral drugs and methods for virus detection requires a comprehensive analysis of the hiv genomic diversity, particularly in the binding sites of oligonucleotides. here, we describe a versatile online database (hivoligodb) with oligonucleotides selected for the diagnosis of hiv and treatment of aids. currently, the data ...201728365729
hiv-2 epidemic in spain - challenges and missing opportunities.: hiv type 2 (hiv-2) is a neglected virus despite estimates of 1-2 million people infected worldwide. hiv-2 is less efficiently transmitted than hiv-1 by sex and from mother-to-child. although aids may develop in hiv-2 carriers, it takes longer than in hiv-1-infected patients. in contrast with hiv-1 infection, there is no global pandemic caused by hiv-2, remaining the virus largely confined to west africa. in a less extent and due to socioeconomic ties and wars, hiv-2 is prevalent in portugal an ...201728358736
cyclophilins and nucleoporins are required for infection mediated by capsids from circulating hiv-2 primary isolates.hiv-2 groups have emerged from sooty mangabey siv and entered the human population in africa on several separate occasions. compared to world pandemic hiv-1 that arose from the chimpanzee sivcpz virus, the sivsm-derived hiv-2, largely confined to west africa, is less replicative, less transmissible and less pathogenic. here, we evaluated the interactions between host cellular factors, which control hiv-1 infection and target the capsid, and hiv-2 capsids obtained from primary isolates from patie ...201728345672
fidelity of classwide-resistant hiv-2 reverse transcriptase and differential contribution of k65r to the accuracy of hiv-1 and hiv-2 reverse transcriptases.nucleoside reverse transcriptase (rt) inhibitors constitute the backbone of current therapies against human immunodeficiency virus type 1 and type 2 (hiv-1 and hiv-2, respectively). however, mutational pathways leading to the development of nucleoside analogue resistance are different in both types of hiv. in hiv-2, resistance to all approved nucleoside analogues is conferred by the combination of rt substitutions k65r, q151m and m184v. nucleotide incorporation kinetic analyses of mutant and wil ...201728333133
hiv diagnosis and treatment through advanced technologies.human immunodeficiency virus (hiv) is the chief contributor to global burden of disease. in 2010, hiv was the fifth leading cause of disability-adjusted life years in people of all ages and leading cause for people aged 30-44 years. it is classified as a member of the family retroviridae and genus lentivirus based on the biological, morphological, and genetic properties. it infects different cells of the immune system, such as cd4+ t cells (t-helper cells), dendritic cells, and macrophages. hiv ...201728326304
insight into hiv-2 latency may disclose strategies for a cure for hiv-1 infection.hiv-1 and hiv-2 originate from two distinct zoonotic transmissions of simian immunodeficiency viruses from primate to human. although both share similar modes of transmission and can result in the development of aids with similar clinical manifestations, hiv-2 infection is generally milder and less likely to progress to aids. hiv is currently incurable due to the presence of hiv provirus integrated into the host dna of long-lived memory cells of the immune system without active replication. as s ...201728275453
rna-associated early-stage anti-viral factor (reaf) is a major component of lv2 restriction.hiv and siv replication in human cells is restricted at early post-entry steps by host inhibitory factors. we previously described and characterised an early phase restriction of hiv-1 and 2 replication in human cell lines, primary macrophages and pbmcs. the restriction was termed lentiviral restriction 2 (lv2). the viral determinants of lv2 susceptibility mapped to the hiv-2 env and ca. we subsequently reported a whole genome sirna screen for factors involved in to hiv which identified rna-asso ...201728275184
primate lentiviruses modulate nf-κb activity by multiple mechanisms to fine-tune viral and cellular gene expression.the transcription factor nuclear factor kappa-light-chain-enhancer of activated b cells (nf-κb) plays a complex role during the replication of primate lentiviruses. on the one hand, nf-κb is essential for induction of efficient proviral gene expression. on the other hand, this transcription factor contributes to the innate immune response and induces expression of numerous cellular antiviral genes. recent data suggest that primate lentiviruses cope with this challenge by boosting nf-κb activity ...201728261165
an unexpected diagnosis of human immunodeficiency virus-2 infection in an overseas visitor: a case report.human immunodeficiency virus 2 infection is endemic in west africa but is also found in parts of europe, north and south america, and india where it is thought to have been introduced secondary to migration and commercial trade ties. it is less common than human immunodeficiency virus 1, with differences in pathogenicity, lower rates of transmission, longer asymptomatic period and slower progression to acquired immunodeficiency syndrome. human immunodeficiency virus 2 is also associated with dia ...201728259182
interleukin-27 enhances the potential of reactive oxygen species generation from monocyte-derived macrophages and dendritic cells by induction of p47(phox).interleukin (il)-27, a member of the il-12 cytokine family, plays an important and diverse role in the function of the immune system. we have previously demonstrated that il-27 is an anti-viral cytokine which inhibits hiv-1, hiv-2, influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ros) generating activity during differentiation of monocytes to macrophages. in this study, we further investigated the mechanism of the enhanced potential for r ...201728240310
vpx overcomes a samhd1-independent block to hiv reverse transcription that is specific to resting cd4 t cells.early after entry into monocytes, macrophages, dendritic cells, and resting cd4 t cells, hiv encounters a block, limiting reverse transcription (rt) of the incoming viral rna genome. in this context, dntp triphosphohydrolase sam domain and hd domain-containing protein 1 (samhd1) has been identified as a restriction factor, lowering the concentration of dntp substrates to limit rt. the accessory lentiviral protein x (vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, so ...201728228523
different expression of interferon-stimulated genes in response to hiv-1 infection in dendritic cells based on their maturation state.dendritic cells (dcs) are professional antigen-presenting cells whose functions are dependent on their degree of differentiation. in their immature state, dcs capture pathogens and migrate to the lymph nodes. during this process, dcs become resident mature cells specialized in antigen presentation. dcs are characterized by a highly limiting environment for human immunodeficiency virus type 1 (hiv-1) replication due to the expression of restriction factors such as samhd1 and apobec3g. however, un ...201728148784
phylogenetic analysis of human immunodeficiency virus type 2 group b.human immunodeficiency virus type 2 (hiv-2) infections are mainly restricted to west africa; however, in the recent years, the prevalence of hiv-2 is a growing concern in some european countries and the southwestern region of india. despite the presence of different hiv-2 groups, only a and b groups have established human-to-human transmission chains.201727621561
biased nucleotide composition and differential codon usage pattern in hiv-1 and hiv-2.hiv-1 and hiv-2 are closely related retroviruses with differences in pathogenicity and geographic distribution. hiv-2 infection is associated with slower disease progression and transmission, longer latency period, low or undetectable plasmatic viral loads, and reduced likelihood of progression to aids, compared to hiv-1. in this investigation, we analyzed hiv-2 genes and genomes and compared them with that of hiv-1 belonging to various subtypes. comparative analysis of the effective number of c ...201727599904
a helical short-peptide fusion inhibitor with highly potent activity against human immunodeficiency virus type 1 (hiv-1), hiv-2, and simian immunodeficiency virus.human immunodeficiency virus type 2 (hiv-2) has already spread to different regions worldwide, and currently about 1 to 2 million people have been infected, calling for new antiviral agents that are effective on both hiv-1 and hiv-2 isolates. t20 (enfuvirtide), a 36-mer peptide derived from the c-terminal heptad repeat region (chr) of gp41, is the only clinically approved hiv-1 fusion inhibitor, but it easily induces drug resistance and is not active on hiv-2. in this study, we first demonstrate ...201727795437
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
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