Sequence Conservation and Antibody Cross‐Recognition of Clade B Human Immunodeficiency Virus (HIV) Type 1 Tat Protein in HIV‐1–Infected Italians, Ugandans, and South Africans

Introduction. Tat protein is a major factor of HIV (human immunodeficiency virus) transcription regulation and has other activities. Tat is characterized by high variability, with some amino acid substitutions, including subtypespecific ones, being able to influence on its functionality. HIV type 1 (HIV-1) sub-subtype A6 is the most widespread in Russia. Previous studies of the polymorphisms in structural regions of the A6 variant have shown numerous characteristic features; however, Tat polymorphism in A6 has not been studied.Goals and tasks. The main goal of the work was to analyze the characteristics of Tat protein in HIV-1 A6 variant, that is, to identify substitutions characteristic for A6 and A1 variants, as well as to compare the frequency of mutations in functionally significant domains in sub-subtype A6 and subtype B.Material and methods. The nucleotide sequences of HIV-1 sub-subtypes A6, A1, A2, A3, A4, subtype B and the reference nucleotide sequence were obtained from the Los Alamos international database.Results and discussion. Q54H and Q60H were identified as characteristic substitutions. Essential differences in natural polymorphisms between sub-subtypes A6 and A1 have been demonstrated. In the CPP-region, there were detected mutations (R53K, Q54H, Q54P, R57G) which were more common in sub-subtype A6 than in subtype B.Conclusion. Tat protein of sub-subtype A6 have some characteristics that make it possible to reliably distinguish it from other HIV-1 variants. Mutations identified in the CPP region could potentially alter the activity of Tat. The data obtained could form the basis for the drugs and vaccines development.

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Faculty Opinions recommendation of Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1006121.76307 ◽

2002 ◽

Author(s):

William Evan Secor

Keyword(s):

Human Immunodeficiency Virus ◽

Disease Progression ◽

Large Cohort ◽

Immunodeficiency Virus ◽

Hiv Type 1 ◽

Hiv 1

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The Human Immunodeficiency Virus Type 1 Tat Protein Up-Regulates the Promoter Activity of the Beta-Chemokine Monocyte Chemoattractant Protein 1 in the Human Astrocytoma Cell Line U-87 MG: Role of SP-1, AP-1, and NF-κB Consensus Sites

Journal of Virology ◽

10.1128/jvi.74.4.1632-1640.2000 ◽

2000 ◽

Vol 74 (4) ◽

pp. 1632-1640 ◽

Cited By ~ 70

Author(s):

Siew Pheng Lim ◽

Alfredo Garzino-Demo

Keyword(s):

Human Immunodeficiency Virus ◽

Promoter Activity ◽

Tat Protein ◽

Monocyte Chemoattractant Protein 1 ◽

Monocyte Chemoattractant ◽

Monocyte Chemoattractant Protein ◽

Astrocytoma Cell ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT It has been shown that the human immunodeficiency virus type 1 (HIV-1) Tat protein can specifically enhance expression and release of monocyte chemoattractant protein 1 (MCP-1) from human astrocytes. In this study, we show evidence that Tat-induced MCP-1 expression is mediated at the transcriptional level. Transient transfection of an expression construct encoding the full-length Tat into the human glioblastoma-astrocytoma cell line U-87 MG enhances reporter gene activity from cotransfected deletion constructs of the MCP-1 promoter. HIV-1 Tat exerts its effect through a minimal construct containing 213 nucleotides upstream of the translational start site. Site-directed mutagenesis studies indicate that an SP1 site (located between nucleotides −123 and −115) is critical for both constitutive and Tat-enhanced expression of the human MCP-1 promoter, as mutation of this SP1 site significantly diminished reporter gene expression in both instances. Gel retardation experiments further demonstrate that Tat strongly enhances the binding of SP1 protein to its DNA element on the MCP-1 promoter. Moreover, we also observe an increase in the binding activities of transcriptional factors AP1 and NF-κB to the MCP-1 promoter following Tat treatment. Mutagenesis studies show that an upstream AP1 site and an adjacent NF-κB site (located at −128 to −122 and −150 to −137, respectively) play a role in Tat-mediated transactivation. In contrast, a further upstream AP1 site (−156 to −150) does not appear to be crucial for promoter activity. We postulate that a Tat-mediated increase in SP1 binding activities augments the binding of AP1 and NF-κB, leading to synergistic activation of the MCP-1 promoter.

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Membrane-Anchored Peptide Inhibits Human Immunodeficiency Virus Entry

Journal of Virology ◽

10.1128/jvi.75.6.3038-3042.2001 ◽

2001 ◽

Vol 75 (6) ◽

pp. 3038-3042 ◽

Cited By ~ 78

Author(s):

Markus Hildinger ◽

Matthias T. Dittmar ◽

Patricia Schult-Dietrich ◽

Boris Fehse ◽

Barbara S. Schnierle ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Helper ◽

Immunodeficiency Virus ◽

Retrovirus Vector ◽

Human Immunodeficiency Virus Entry ◽

Hiv Type 1 ◽

Heptad Repeats ◽

Hiv 1 ◽

Gp41 Envelope

ABSTRACT Peptides derived from the heptad repeats of human immunodeficiency virus (HIV) gp41 envelope glycoprotein, such as T20, can efficiently inhibit HIV type 1 (HIV-1) entry. In this study, replication of HIV-1 was inhibited more than 100-fold in a T-helper cell line transduced with a retrovirus vector expressing membrane-anchored T20 on the cell surface. Inhibition was independent of coreceptor usage.

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Effect of Human Immunodeficiency Virus (HIV) Type 1 Viral Genotype on Mother‐to‐Child Transmission of HIV‐1

The Journal of Infectious Diseases ◽

10.1086/315252 ◽

2000 ◽

Vol 181 (2) ◽

pp. 746-749 ◽

Cited By ~ 24

Author(s):

Melanie C. M. Murray ◽

Joanne E. Embree ◽

Sue G. Ramdahin ◽

Aggrey O. Anzala ◽

Simon Njenga ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Mother To Child Transmission ◽

Viral Genotype ◽

Child Transmission ◽

Immunodeficiency Virus ◽

Hiv Type 1 ◽

Mother To Child ◽

Hiv 1

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Tat Protein of Human Immunodeficiency Virus Type 1 Subtype C Strains Is a Defective Chemokine

Journal of Virology ◽

10.1128/jvi.78.5.2586-2590.2004 ◽

2004 ◽

Vol 78 (5) ◽

pp. 2586-2590 ◽

Cited By ~ 114

Author(s):

Udaykumar Ranga ◽

Raj Shankarappa ◽

Nagadenahalli B. Siddappa ◽

Lakshmi Ramakrishna ◽

Ramalingam Nagendran ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

The United States ◽

Tat Protein ◽

Subtype C ◽

Monocyte Migration ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is correlated with increased monocyte migration to the brain, and the incidence of HAD among otherwise asymptomatic subjects appears to be lower in India than in the United States and Europe (1 to 2% versus 15 to 30%). Because of the genetic differences between HIV-1 strains circulating in these regions, we sought to identify viral determinants associated with this difference. We targeted Tat protein for these studies in view of its association with monocyte chemotactic function. Analyses of Tat sequences representing nine subtypes revealed that at least six amino acid residues are differentially conserved in subtype C Tat (C-Tat). Of these, cysteine (at position 31) was highly (>99%) conserved in non-subtype C viruses and more than 90% of subtype C viruses encoded a serine. We hypothesized a compromised chemotactic function of C-Tat due to the disruption of CC motif and tested it with the wild type C-Tat (CS) and its two isogenic variants (CC and SC) derived by site-directed mutagenesis. We found that the CS natural variant was defective for monocyte chemotactic activity without a loss in the transactivation property. While the CC mutant is functionally competent for both the functions, in contrast, the SC mutant was defective in both. Therefore, the loss of the C-Tat chemotactic property may underlie the reduced incidence of HAD; although not presenting conclusive evidence, this study provides the first evidence for a potential epidemiologic phenomenon associated with biological differences in the subtype C viruses.

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The Human Immunodeficiency Virus Type 1 Tat Protein Enhances Cryptosporidium parvum-Induced Apoptosis in Cholangiocytes via a Fas Ligand-Dependent Mechanism

Infection and Immunity ◽

10.1128/iai.01348-06 ◽

2006 ◽

Vol 75 (2) ◽

pp. 684-696 ◽

Cited By ~ 9

Author(s):

Steven P. O'Hara ◽

Aaron J. Small ◽

Jeremy B. Nelson ◽

Andrew D. Badley ◽

Xian-Ming Chen ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Cryptosporidium Parvum ◽

Fas Ligand ◽

Tat Protein ◽

Immunodeficiency Virus ◽

Induced Apoptosis ◽

Hiv 1 ◽

Dependent Mechanism

ABSTRACT While Cryptosporidium parvum infection of the intestine has been reported in both immunocompetent and immunocompromised individuals, biliary infection is seen primarily in adult AIDS patients and is associated with development of AIDS cholangiopathy. However, the mechanisms of pathogen-induced AIDS cholangiopathy remain unclear. Since we previously demonstrated that the Fas/Fas ligand (FasL) system is involved in paracrine-mediated C. parvum cytopathicity in cholangiocytes, we also tested the potential synergistic effects of human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat)-mediated FasL regulation on C. parvum-induced apoptosis in cholangiocytes by semiquantitative reverse transcription-PCR, immunoblotting, immunofluorescence analysis, and immunogold electron microscopy. H69 cells do not express CXCR4 and CCR5, which are receptors required for direct HIV-1 viral infection. However, recombinant biologically active HIV-1-associated Tat protein increased FasL expression in the cytoplasm of cholangiocytes without a significant increase in apoptosis. We found that C. parvum-induced apoptosis was associated with translocation of intracellular FasL to the cell membrane surface and release of full-length FasL from infected H69 cells. Tat significantly (P < 0.05) increased C. parvum-induced apoptosis in bystander cells in a dose-dependent manner. Moreover, Tat enhanced both C. parvum-induced FasL membrane translocation and release of full-length FasL. In addition, the FasL neutralizing antibody NOK-1 and the caspase-8 inhibitor Z-IETD-fmk both blocked C. parvum-induced apoptosis in cholangiocytes. The data demonstrated that HIV-1 Tat enhances C. parvum-induced cholangiocyte apoptosis via a paracrine-mediated, FasL-dependent mechanism. Our results suggest that concurrent active HIV replication, with associated production of Tat protein, and C. parvum infection synergistically increase cholangiocyte apoptosis and thus jointly contribute to AIDS-related cholangiopathies.

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Cell-Mediated Immune Response to Human Immunodeficiency Virus (HIV) Type 1 in Seronegative Homosexual Men with Recent Sexual Exposure to HIV-1

The Journal of Infectious Diseases ◽

10.1093/infdis/165.6.1012 ◽

1992 ◽

Vol 165 (6) ◽

pp. 1012-1019 ◽

Cited By ~ 256

Author(s):

Mario Clerici ◽

Janis V. Giorgi ◽

Chen-Cheng Chou ◽

Vaheideh K. Gudeman ◽

Jerome A. Zack ◽

...

Keyword(s):

Immune Response ◽

Human Immunodeficiency Virus ◽

Homosexual Men ◽

Cell Mediated Immune Response ◽

Immunodeficiency Virus ◽

Hiv Type 1 ◽

Hiv 1

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A functional genetic approach suggests a novel interaction between the human immunodeficiency virus type 1 (HIV-1) Tat protein and HIV-1 TAR RNA in vivo

Journal of General Virology ◽

10.1099/vir.0.18645-0 ◽

2003 ◽

Vol 84 (3) ◽

pp. 603-606 ◽

Cited By ~ 5

Author(s):

Lars H. Lund ◽

Britta Wahren ◽

Mariano A. Garcia-Blanco

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Tat Protein ◽

Cyclin T1 ◽

Immunodeficiency Virus ◽

Tar Rna ◽

Hiv 1

Human immunodeficiency virus type 1 (HIV-1) Tat and human Cyclin T1 form a complex and together recognize the viral TAR RNA element with specificity. Using HIV-1/equine infectious anaemia virus TAR chimeras, we show that in addition to the well-characterized interaction with the bulge, Tat recognizes the distal stem and the loop of TAR. These data support previously proposed, but unproven, molecular models.

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Effects of Tat proteins and Tat mutants of different human immunodeficiency virus type 1 clades on glial JC virus early and late gene transcription

Journal of General Virology ◽

10.1099/vir.0.047902-0 ◽

2013 ◽

Vol 94 (3) ◽

pp. 514-523 ◽

Cited By ~ 4

Author(s):

Clayton A. Wright ◽

Jonas A. Nance ◽

Edward M. Johnson

Keyword(s):

Human Immunodeficiency Virus ◽

Dna Replication ◽

Gene Transcription ◽

Cellular Proteins ◽

Late Gene ◽

Clade B ◽

Immunodeficiency Virus ◽

The Brain ◽

Hiv 1

Polyomavirus JC (JCV) is the aetiological agent of progressive multifocal leukoencephalopathy (PML), a frequently fatal infection of the brain afflicting nearly 4 % of AIDS patients in the USA. Human immunodeficiency virus type 1 (HIV-1) Tat, acting together with cellular proteins at the JCV non-coding control region (NCCR), can stimulate JCV DNA transcription and replication. Tat in the brain is secreted by HIV-1-infected cells and incorporated by oligodendroglia, cells capable of infection by JCV. Thus far the effects of Tat on JCV have been studied primarily with protein encoded by the HIV-1 B clade most common in North America. Here, we determine the abilities of Tat from different HIV-1 clades to alter JCV early and late gene transcription and DNA replication initiated at the JCV origin. Tat from all clades tested stimulates both JCV early and late gene promoters, with clade B Tat being significantly most effective. Tat proteins from the HIV-1 clades display parallel patterns of differences in their effects on HIV-1 and JCV transcription, suggesting that Tat effects in both cases are mediated by the same cellular proteins. Clade B Tat is most effective at directing Smad mediators of tumour growth factor beta and cellular partner Purα to the NCCR. Tat proteins from all non-B clades inhibit initiation of JCV DNA replication. The effectiveness of HIV-1 clade B Tat at promoting JCV transcriptional and replicative processes highlights a need for further investigation to determine which molecular aspects of Tat from distinct HIV-1 substrains can contribute to the course of PML development in neuroAIDS.

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