Human Immune Deficiency Virus-1 Research Articles

Graphene nanoribbon derived from multi-walled carbon nanotube: An efficient viral gene hosting and biosensing molecular platform for the electroanalysis of HIV-1 gene

Graphene nanoribbon (GNR) is a carbon nanomaterial with strikingly distinct characteristics compared to graphene. GNRs possess high aspect ratio, variable band gap, high surface area and high density of reactive edge states which make it an emerging flat molecular platform alternative to graphene. GNR is not much explored in sensing applications compared to graphene. Here, for the first time, we are reporting the application of GNRs, derived from multiwalled carbon nanotube (MWCNT), as an efficient flat molecular platform for hosting and biosensing of Human immune deficiency virus-1 (HIV-1) gene. For the construction of HIV-1 sensor, GNRs were synthesized by unzipping of MWCNTs and deposited onto glassy carbon electrode (GCE) followed by the immobilization of HIV-1 probe (ssDNA) onto the resulting GCE/GNR platform to obtain GCE/GNR/ssDNA sensor. Subsequently, the sensor was employed in the analysis of target gene (cDNA) by measuring the voltammetric response generated from hybridization between ssDNA and cDNA. Differential pulse voltammetry (DPV) responses recorded at different target gene concentrations displayed perfect linear correlation (R2 = 0.991). The sensor exhibited low detection limit (2.3 aM), low quantification limit (7.67 aM) and high sensitivity (5.5 μA aM−1 cm−2) which is possibly due to synergic effects of GNRs. Sensor exhibited acceptable stability, repeatability and displayed good selectivity when tested with mismatched target DNA sequences. Further, sensor’s diagnostic applicability was verified by spiking target gene in human blood sample which showed high recovery (4 %) indicating its practical utility in the electroanalysis of HIV-1 gene in human blood samples.

COVID-19 Outcomes in Patients With Uncontrolled HIV-1 Infection.

COVID-19 Outcomes in Patients With Uncontrolled HIV-1 Infection.

NiCo2O4 spinel embedded with carbon nanotubes derived from bimetallic NiCo metal-organic framework for the ultrasensitive detection of human immune deficiency virus-1 gene

A bimetallic NiCo-based metal-organic framework (NiCo-MOF) was pyrolyzed into a novel composite comprising NiCo2O4 spinel, CoO, and metallic Co/Ni nanoparticles embedded with carbon nanotubes at high temperature 700 °C under N2 atmosphere (represented by NiCo2O4/CoO@CNTs), whereas organic ligands were almost decomposed in H2 atmosphere, leading to absence of carbon nanotubes (denoted by NiCo2O4/CoO). The feasibility of using the composite as efficient bioplatform for immobilizing the probe DNA of human immune deficiency virus-1 (HIV-1) in the electrochemical detection of the HIV-1 DNA was explored. Compared with the pristine NiCo-MOF and NiCo2O4/CoO, the NiCo2O4/CoO@CNTs composite exhibited high electrochemical activity, good biocompatibility, and strong bioaffinity toward the probe DNA. Electrochemical measurements demonstrated that the NiCo2O4/CoO@CNTs-based bioassay displayed superior sensing performances, giving an ultralow detection limit of 16.7 fM toward HIV-1 DNA over the linear range of 0.1 pM to 20 nM; possessing high selectivity even against noncomplementary and two-base mismatch sequences; exhibiting good stability, reproducibility, repeatability and applicability in the application of detecting human serum samples. Thus, the present strategy can broaden the application of MOFs and their derivatives in various fields of biosensing.

Study of Patterns and Markers of Human Immune Deficiency Virus -1 (HIV-1) Progression and Unemployment Rate among Patients from Alexandria, Egypt.

Middle East and North Africa (MENA) new HIV cases show the highest increase among all regions in the world. Even though Egypt has a low prevalence among the general population (< 0.02%), a national HIV epidemic occurs in certain population risk groups. The current study was conducted to asses clinical and immunological disease progression; following up viral load (VL) and detecting delta-32 CCR5 genotype polymorphism in selected cases, determining unemployment rate and identify predictors of employment for HIV-cases. A cross sectional design was adopted. HIV infected cases attending Alexandria Fever Hospital (AFH) for one year. Interview questionnaire and four CD+4 counts were done for all patients, HIV VL and delta-32 CCR5 polymorphism were done for selected cases. Sexual transmission and drug abuse are the most important risk factors. Infectious comorbidity increases the rate of HIV progression. CD4+ count at the end of the study; CD+4 (4), count was significantly higher than all other CD4+ readings among the whole cohort and among the treated group. Also, VL at the end of the study; VL(2), was significantly higher than VL(1) among the untreated group. Unemployment rate was 40%. Male gender and obtaining vocational training were significant predictors of employment. It can be concluded that having a family member living with HIV and drug abusers are high risk groups for HIV acquisition. Factors responsible for progression of HIV should be further investigated. Antiretroviral therapy is very effective in checking HIV replication rate, delaying the progression of HIV, reconstituting the immune response and should be available for all cases detected.

Signaling and Polarized Communication Across the T Cell Immunological Synapse.

T cells express a somatically recombined antigen receptor (αβTCR) that is calibrated during development to respond to changes in peptides displayed by major histocompatibility complex proteins (pMHC) on the surface of antigen-presenting cells (APC). A key characteristic of pMHC for adaptive immunity is the ability to sample internal states of cells and tissues to sensitively detect changes associated with infection, cell derangement, or tissue injury. Physical T cell-APC contact sets up an axis for polarization of TCR, adhesion molecules, kinases, cytoskeletal elements, and organelles inherent in this mode of juxtacrine signaling. The discovery of further lateral organization of the TCR and adhesion molecules into radially symmetric compartments, the immunological synapse, revealed an intersecting plane of symmetry and potential for regulated symmetry breaking to control duration of T cell-APC interactions. In addition to organizing signaling machinery, the immunological synapse directs the polarized transport and secretion of cytokines and cytolytic agents across the synaptic cleft and is a site for the generation and exocytic release of bioactive microvesicles that can functionally affect recipient APC and other cells in the environment. This machinery is coopted by retroviruses, and human immune deficiency virus-1 may even use antigen-specific synapses for infection of healthy T cells. Here, we discuss recent advances in the molecular and cell biological mechanisms of immunological synapse assembly and signaling and its role in intercellular communication across the synaptic cleft.

Context Surrounding Processing Sites Is Crucial in Determining Cleavage Rate of a Subset of Processing Sites in HIV-1 Gag and Gag-Pro-Pol Polyprotein Precursors by Viral Protease

Processing of the human immunodeficiency virus type 1 (HIV-1) Gag and Gag-Pro-Pol polyproteins by the HIV-1 protease (PR) is essential for the production of infectious particles. However, the determinants governing the rates of processing of these substrates are not clearly understood. We studied the effect of substrate context on processing by utilizing a novel protease assay in which a substrate containing HIV-1 matrix (MA) and the N-terminal domain of capsid (CA) is labeled with a FlAsH (fluorescein arsenical hairpin) reagent. When the seven cleavage sites within the Gag and Gag-Pro-Pol polyproteins were placed at the MA/CA site, the rates of cleavage changed dramatically compared with that of the cognate sites in the natural context reported previously. The rate of processing was affected the most for three sites: CA/spacer peptide 1 (SP1) (≈10-fold increase), SP1/nucleocapsid (NC) (≈10-30-fold decrease), and SP2/p6 (≈30-fold decrease). One of two multidrug-resistant (MDR) PR variants altered the pattern of processing rates significantly. Cleavage sites within the Pro-Pol region were cleaved in a context-independent manner, suggesting for these sites that the sequence itself was the determinant of rate. In addition, a chimera consisting of SP1/NC P4-P1 and MA/CA P1'-P4' residues (ATIM↓PIVQ) abolished processing by wild type and MDR proteases, and the reciprocal chimera consisting of MA/CA P4-P1 and SP1/NC P1'-4' (SQNY↓IQKG) was cleaved only by one of the MDR proteases. These results suggest that complex substrate interactions both beyond the active site of the enzyme and across the scissile bond contribute to defining the rate of processing by the HIV-1 PR.

RETRACTED ARTICLE: Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

BackgroundCognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers and a deficit of synaptic proteins.MethodsWe measured protein and mRNA levels of markers of neuroinflammation and the AA cascade, as well as pro-apoptotic factors and synaptic proteins, in brains from 7- to 9-month-old HIV-1 Tg and control rats.ResultsCompared with control brain, HIV-1 Tg rat brain showed immunoreactivity to glycoprotein 120 and tat HIV-1 viral proteins, and significantly higher protein and mRNA levels of (1) the inflammatory cytokines interleukin-1β and tumor necrosis factor α, (2) the activated microglial/macrophage marker CD11b, (3) AA cascade enzymes: AA-selective Ca2+-dependent cytosolic phospholipase A2 (cPLA2)-IVA, secretory sPLA2-IIA, cyclooxygenase (COX)-2, membrane prostaglandin E2 synthase, 5-lipoxygenase (LOX) and 15-LOX, cytochrome p450 epoxygenase, and (4) transcription factor NF-κBp50 DNA binding activity. HIV-1 Tg rat brain also exhibited signs of cell injury, including significantly decreased levels of brain-derived neurotrophic factor (BDNF) and drebrin, a marker of post-synaptic excitatory dendritic spines. Expression of Ca2+-independent iPLA2-VIA and COX-1 was unchanged.ConclusionsHIV-1 Tg rats show elevated brain markers of neuroinflammation and AA metabolism, with a deficit in several synaptic proteins. These changes are associated with viral proteins and may contribute to cognitive impairment. The HIV-1 Tg rat may be a useful model for understanding progression and treatment of cognitive impairment in HIV-1 patients.

Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?

Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.

Molecular programming of endothelin‐1 in HIV‐infected brain: role of Tat in up‐regulation of ET‐1 and its inhibition by statins

Human Immune Deficiency Virus-1 (HIV-1) infection can induce severe and debilitating neurological problems, including behavioral abnormalities, motor dysfunction, and dementia. HIV can persistently infect astrocytes, during which viral accessory proteins are produced that are unaffected by current antiretroviral therapy. The effect of these proteins on astrocyte function remains unknown. Astrocytes are the predominant cells within the brain; thus, disruption of astrocyte function could influence the neuropathogenesis of HIV infection. To explore further these effects, we constitutively expressed HIV-Tat protein in astrocytes. Since the nuclear presence of Tat protein leads to alteration of host gene expression, we further analyzed the effects of Tat on host gene transcripts. Endothelin-1 (ET-1) was a significantly elevated transcript as verified by reverse transcription-polymerase chain reaction (RT-PCR), and it was subsequently released extracellularly in Tat-expressing and HIV-infected astrocytes. ET-1 expression was also prominent in reactive astrocytes and neurons in brain tissues from basal ganglia and frontal lobes of HIV encephalitic patients. HIV-Tat regulated ET-1 at the transcriptional level through NF-kappaB (NF-kappaB)-responsive sites in the ET-1 promoter. Intriguingly, simvastatin (10 microM) down-regulated HIV-Tat-induced ET-1 and also inhibited activation of NF-kappaB in astrocytes. Our findings suggest that ET-1 may be critical in mediating the neuropathogenesis of HIV dementia and that statins may have therapeutic potential in these patients.

Protein imaging on a semiconducting substrate: A scanning tunnelling microscopy investigation

The reverse transcriptase (RT) enzymes of the human immune deficiency virus 1 (HIV-1) and of the avian myeloblastosis virus (AMV) are deposited onto the semiconducting substrate n-MoTe2 and imaged by scanning tunnelling microscopy (STM). Molecule selection was made after considering the unique complex and specific enzyme structures and medical relevance. Protein immobilization is attributed to specific substrate structural defects and localized electrostatic interaction. The ultrastructure resolution obtained is ascribed to energetic and charge transfer properties of metal tip/protein/semiconductor contacts with an energetic shift of semiconductor band edges due to (partial) Fermi level pinning and/or formation and reversal of a strong inversion layer. Protein electron transport combining Poole–Frenkel-type transport in insulators and solvation-induced electron detrapping is suggested.

Human Immune Deficiency Virus-1: Diagnosis and Treatment in Adults and Adolescents

Human Immune Deficiency Virus-1: Diagnosis and Treatment in Adults and Adolescents

CCR2 polymorphisms affect neuropsychological impairment in HIV-1-infected adults

CCR2 is a minor coreceptor for human immune deficiency virus-1 (HIV-1) and its impact on HIV-1-related neuropsychological impairment (NPI) remains unknown. We studied the impact of CCR2-V64I polymorphisms on the development of NPI in 121 HIV-1 patients. The CCR2-64-I allele was associated with rate of progression to NPI when measured from the first study visit (Log Rank p=0.01) or from the estimated time of seroconversion ( p=0.02). CCR2-V64I was not associated with plasma or CSF HIV-1 RNA load, suggesting that the impact of CCR2 on neuropathogenesis may involve alterations in inflammatory responses within the CNS rather than a direct impact on viral entry or replication.

Current status and potential application of ISCOMs in veterinary medicine

The immune stimulating complex (ISCOM) is a 40 nm nanoparticle used as a delivery system for vaccine antigens, targeting the immune system both after parenteral and mucosal administration. The ISCOM is made up of saponin, lipids and antigen usually held together by hydrophobic interaction between these three components. The compulsory elements to form the ISCOM structure are cholesterol and saponin. When the antigen is omitted the ISCOM-MATRIX is formed. There are a number of saponins that can form ISCOMs, and many other substances (including antigens, targeting and immuno-modulating molecules) can be incorporated into the ISCOM provided they are hydrophobic or rendered to be hydrophobic. Thus, it is possible to create ISCOM particles with different properties. After parenteral immunisation of the ISCOM, the T cell response is first detected in the draining lymph node. Subsequently, the T cell response is localised to the spleen, while the B cell response is first found both in the draining lymph nodes and in the spleen. Up to 50 days later, the majority of the antibody producing cells is found in the bone marrow (BM). In contrast, antigens that have been adjuvanted in an oil emulsion, limit the T cell response to the draining lymph nodes while the B cell response is found in the draining lymph nodes and spleen, but not in the BM. The ISCOM efficiently evokes CD8+, MHC class 1 restricted T cell response. The deposit of antigens both to the endosomal vesicles and to the cytosol of antigen presenting cells (APCs) explains why both T helper cells (vesicles) and cytotoxic T lymphocytes (cytosol) are efficiently induced by ISCOMs. The T helper (Th) cell response is balanced in the sense that both Th1 and Th2 cells are induced. Prominent IL-12 production by cells in the innate system is a characteristic reaction induced by ISCOMs, promoting the development of a strong Th1 response. After mucosal administration by the intranasal or the intestinal routes, the ISCOM induces strong specific mucosal IgA responses in local and remote mucosal surfaces. Also T cell responses are evoked by the mucosal administration. A large number of experimental ISCOM vaccines have been tested and protection has been induced against a number of pathogens in various species including chronic and persistent infections exemplified by human immune deficiency virus 1 (HIV-1), and 2 (HIV-2) and simian immune deficiency virus (SIV) in primates, and various herpes virus infections in several species. In contrast to a conventional rabies virus vaccine the ISCOM rabies formulation protected mice after exposure to the virulent virus. Recently, experimental ISCOM vaccines were shown to efficiently induce immune response in newborns of murine and bovine species in the presence of maternal antibodies, while conventional vaccines have failed. ISCOM vaccines are on the market for horses and cattle and several other ISCOM vaccines are under development. Since the ISCOM and the ISCOM-MATRIX can be blended with live attenuated vaccine antigens without hampering the proliferation of the live vaccine antigens, it opens the possibility to use the ISCOM adjuvant system in a mixture of live and killed vaccine antigens.

Human immunodeficiency virus-1 infection and multiple sclerosis-like illness in a child

We present a child with human immune deficiency virus-1 infection associated with a multiple sclerosis-like illness. This case is the first reported of human immune deficiency virus-1 infection and a disease indistinguishable from multiple sclerosis in a child. Because of the rarity of either disease in pediatric patients, their coexistence in a child argues in favor of a casual association between the two illnesses, thus reinforcing the long-held assumption that viral agents may trigger some of the immunologic abnormalities underlying multiple sclerosis. Cases in which such an association was present in adults are also described in this article.

Virus inactivation of blood products by phenothiazine dyes and light.

Methylene blue (MB) and its derivatives azure A, B, C and thionine are photoactive and, in principle, are suitable for photodynamic virus inactivation of blood and blood products, such as therapeutic plasma. Methylene blue was selected for plasma decontamination because it is being clinically used and because of its known toxicological and other properties. The standard procedure for photodynamic treatment of single units of fresh plasma involves illumination with visible light at an MB concentration of 1 microM. Polymerase chain reaction analysis revealed that, in addition to model viruses, the bloodborne viruses hepatitis B virus, hepatitis C virus, human immune deficiency virus-1 and probably also the nonenveloped parvovirus B19 are sensitive to MB/light treatment. The procedure is further improved when the fluorescent tubes routinely used for illumination are replaced by more intense light sources, e.g. light-emitting diodes or low-pressure sodium lamps. Surprisingly, the improved virus kill is accompanied by reduced damage to plasma proteins.

Selective non-nucleoside HIV-1 reverse transcriptase inhibitors. New 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds with anti-HIV-1 activity.

A series of substituted 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones and related compounds 1-73 were synthesized and evaluated for their ability to inhibit reverse transcriptase (RT) of the human immune deficiency virus 1 (HIV-1) and replication of HIV-1 in MT2 cells. The antiviral activity of these compounds depends on the stereoselective configuration of the substituent in position 9b. Structure-activity studies were done within these series of compounds to determine the optimum substituents for antiviral activity. The most potent inhibitors were found in the class of 2,3-dihydrothiazolo[2,3-a]isoindol-5(9bH)-ones bearing a phenyl ring system in position 9b optionally substituted with one or two methyl groups or a chlorine atom in position 8. The most active analogues (R)-(+)-1, (R)-(+)-6, (R)-(+)-13, (R)-(+)-26, and (R)-(+)-53 inhibit the HIV-1 RT with an IC50 between 16 and 300 nM and an IC50 between 10 and 392 nM in MT2 cells, respectively.

Membrane tumour necrosis factor-alpha is involved in the polyclonal B-cell activation induced by HIV-infected human T cells.

Infection of CD4+ T cells by human immune deficiency virus-1 (HIV-1) causes severe dysfunction of cellular immunity, but paradoxically results in intense polyclonal activation of B cells, possibly accounting for both hypergammaglobulinaemia and frequent development of B-cell malignancies seen in HIV-infected patients. We have reported that human CD4+ T-cell clones infected with HIV in vitro markedly stimulate immunoglobulin synthesis by B cells through a non-cognate, contact-dependent mechanism. We show here that HIV-infected T-cell clones do not express the CD40 ligand (CD40L), a molecule critical for non-cognate B-cell activation, but a small proportion of them do express membrane tumour-necrosis factor (TNF)-alpha. The ability of HIV-infected T-cell clones to induce polyclonal B-cell activation appears to be restricted to TNF-alpha-positive T blasts and is inhibited by antibodies against both TNF-alpha and TNF-alpha receptor. Freshly isolated CD4+ T cells from HIV-infected individuals express TNF-alpha on the cell membrane and induce TNF-alpha-mediated immunoglobulin production by B cells. Thus, membrane TNF-alpha seems to be involved in the polyclonal B-cell activation induced by HIV-infected T cells.

Virus inactivated single-donor fresh plasma preparations.

Photodynamic virus inactivation of single units of human fresh plasma in their plastic containers can be achieved by illuminating the plasma with visible light in the presence of low concentrations of one of the phenothiazine dyes methylene blue or toluidine blue. This procedure abrogates the infectivity of numerous lipid-enveloped viruses including that of human immune deficiency virus-1. In contrast, the functional activities and immunological properties of plasma proteins are only moderately influenced. Animal studies and the first clinical data suggest that photodynamically virus inactivated fresh plasma is as well tolerated as conventional fresh frozen plasma.

Synthetic peptides as substrates and inhibitors of human immune deficiency virus-1 protease.

Retroviruses code for a virus-specific protease which is essential for polyprotein processing and viral infectivity. The human immune deficiency virus-1 protease is an aspartic protease of 9 kDa which was synthesized by recombinant DNA technology and arises by autocatalytic processing from a polyprotein precursor which has recently been demonstrated by use of a protease-specific monoclonal antibody. The protease was shown to form dimers. Here we demonstrate that synthetic peptides can be used as both model substrates as well as inhibitors for investigation of the protease. 14 synthetic peptides, 7-18 amino acids in length, containing putative protease cleavage sites of the viral polyprotein gag and pol precursors, have been analyzed with the partially purified protease by the use of high performance liquid chromatography. In seven cases, where cleavage was observed, the length of the peptides did not significantly influence the cleavage efficiencies, heptapeptides being large enough as model substrates. No cleavage was observed with a protein preparation purified in parallel from control bacteria not expressing the human immune deficiency virus-1 protease. The protease was not only able to cut next to a proline but also between other peptides indicating that the proline is not a prerequisite. Three peptides with either reduced bonds at the cleavage site or a substitution by statin were inhibitory while another uncleaved substrate was not. The usefulness of small model substrates for characterization of the protease is further demonstrated by determination of a kinetic optimum pH (3.5-5.5) and incubation temperature (37 degrees C).

Prevalence of hepatitis B markers, antibodies to adult T cell leukemia/lymphoma virus and antibodies to human immune deficiency virus in prostitutes in Fukuoka, Japan.

Prevalence of hepatitis B (HB) markers, antibodies to human T cell leukemia virus (HTLV-1) and antibodies to human immune deficiency virus 1 (HIV-1) in prostitutes working in Fukuoka city were studied. Sera were collected from 237 prostitutes during January-September, 1986. Among them, 9 (3.8%) were HB virus surface-antigen (HBs Ag) positive, of whom, 3 were HBe antigen positive and the remaining 6 were anti-HBe positive. The positive rate of anti-HBs was 34.2%. The incidence of anti-HTLV-1 in the prostitutes was 5.9%. These incidences are considered to be within the usual range in Kyushu district. No seropositive case for anti-HIV was found.