Faculty Opinions recommendation of A limited group of class I histone deacetylases acts to repress human immunodeficiency virus type 1 expression.

2014 ◽  
Author(s):  
Angus Dalgleish
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Histone Deacetylases ◽  
Class I ◽  
Immunodeficiency Virus

scholarly journals A Limited Group of Class I Histone Deacetylases Acts To Repress Human Immunodeficiency Virus Type 1 Expression

2009 ◽  
Vol 83 (10) ◽  
pp. 4749-4756 ◽  
Author(s):  
Kara S. Keedy ◽  
Nancie M. Archin ◽  
Adam T. Gates ◽  
Amy Espeseth ◽  
Daria J. Hazuda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Histone Deacetylases ◽  
Hdac Inhibitors ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Silencing of the integrated human immunodeficiency virus type 1 (HIV-1) genome in resting CD4+ T cells is a significant contributor to the persistence of infection, allowing the virus to evade both immune detection and pharmaceutical attack. Nonselective histone deacetylase (HDAC) inhibitors are capable of inducing expression of quiescent HIV-1 in latently infected cells. However, potent global HDAC inhibition can induce host toxicity. To determine the specific HDACs that regulate HIV-1 transcription, we evaluated HDAC1 to HDAC11 RNA expression and protein expression and compartmentalization in the resting CD4+ T cells of HIV-1-positive, aviremic patients. HDAC1, -3, and -7 had the highest mRNA expression levels in these cells. Although all HDACs were detected in resting CD4+ T cells by Western blot analysis, HDAC5, -8, and -11 were primarily sequestered in the cytoplasm. Using chromatin immunoprecipitation assays, we detected HDAC1, -2, and -3 at the HIV-1 promoter in Jurkat J89GFP cells. Targeted inhibition of HDACs by small interfering RNA demonstrated that HDAC2 and HDAC3 contribute to repression of HIV-1 long terminal repeat expression in the HeLa P4/R5 cell line model of latency. Together, these results suggest that HDAC inhibitors specific for a limited number of class I HDACs may offer a targeted approach to the disruption of persistent HIV-1 infection.

scholarly journals Mutually Exclusive T-Cell Receptor Induction and Differential Susceptibility to Human Immunodeficiency Virus Type 1 Mutational Escape Associated with a Two-Amino-Acid Difference between HLA Class I Subtypes

2006 ◽  
Vol 81 (4) ◽  
pp. 1619-1631 ◽  
Author(s):  
Xu G. Yu ◽  
Mathias Lichterfeld ◽  
Senica Chetty ◽  
Katie L. Williams ◽  
Stanley K. Mui ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Viral Escape ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIPMF). When this epitope is presented by HLA-B*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HLA-B*5703 induces an entirely different, more heterogeneous TCR β-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703+ individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations.

HLA Class I Alleles Associated with Susceptibility or Resistance to Human Immunodeficiency Virus Type 1 Infection among a Population in Chaco Province, Argentina

2000 ◽  
Vol 182 (5) ◽  
pp. 1523-1526 ◽  
Author(s):  
Alicia Habegger de Sorrentino ◽  
Karina Marinic ◽  
Patricia Motta ◽  
Adrián Sorrentino ◽  
Roxana López ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Chaco Province

scholarly journals Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1

2002 ◽  
Vol 76 (16) ◽  
pp. 8276-8284 ◽  
Author(s):  
Jianming Tang ◽  
Shenghui Tang ◽  
Elena Lobashevsky ◽  
Angela D. Myracle ◽  
Ulgen Fideli ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Class I ◽  
Hla Class I Molecules ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

ABSTRACT The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8+ cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log10 VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log10 VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (<10,000 copies per ml) and 3.1% of those with the highest (>100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.

HLA Class I Homozygosity Accelerates Disease Progression in Human Immunodeficiency Virus Type 1 Infection

1999 ◽  
Vol 15 (4) ◽  
pp. 317-324 ◽  
Author(s):  
Jianming Tang ◽  
Caroline Costello ◽  
Ireneus P.M. Keet ◽  
Charles Rivers ◽  
Susan Leblanc ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Class I ◽  
Immunodeficiency Virus

scholarly journals Passive Sexual Transmission of Human Immunodeficiency Virus Type 1 Variants and Adaptation in New Hosts

2006 ◽  
Vol 80 (14) ◽  
pp. 7226-7234 ◽  
Author(s):  
A. J. Frater ◽  
C. T. T. Edwards ◽  
N. McCarthy ◽  
J. Fox ◽  
H. Brown ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immune Escape ◽  
Hla Class I ◽  
Class I ◽  
Dependent Manner ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.

scholarly journals Dynamic Evolution of the Human Immunodeficiency Virus Type 1 Pathogenic Factor, Nef

2006 ◽  
Vol 80 (3) ◽  
pp. 1311-1320 ◽  
Author(s):  
Eduardo O'Neill ◽  
Lillian S. Kuo ◽  
John F. Krisko ◽  
Diana R. Tomchick ◽  
J. Victor Garcia ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mhc Class I ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Early Gene ◽  
Class I ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) early gene product Nef is a multifunctional protein that alters numerous pathways of T-cell function, including endocytosis, signal transduction, vesicular trafficking, and immune modulation, and is a major determinant of pathogenesis. Individual Nef functions include PAK-2 activation, CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, and enhancement of viral particle infectivity. How Nef accomplishes its multiple tasks presents a difficult problem of mechanistic analysis because of the complications associated with multiple, overlapping functional domains in the context of significant sequence variability. To address these issues we determined the conservation of each Nef residue based on 1,643 subtype B Nef sequences. Mutational analysis based on conservative substitutions and Nef sequence data allowed us to search for amino acids on the surface of Nef that are specifically required for PAK-2 activation. We found residues 85, 89, and 191 to be highly significant determinants for Nef's PAK-2 activation function but functionally unlinked to CD4 and MHC class I downregulation or enhancement of infectivity. These residues are not conserved across HIV-1 subtypes but are confined to separate sets of surface elements within a subtype. Thus, L85/H89/F191 and F85/F89/R191 are dominant in subtype B and subtype E or C, respectively. Our results provide support for developing subtype-specific interventions in HIV-1 disease.

scholarly journals Efficient Incorporation of HLA Class II onto Human Immunodeficiency Virus Type 1 Requires Envelope Glycoprotein Packaging

2000 ◽  
Vol 74 (8) ◽  
pp. 3918-3923 ◽  
Author(s):  
Dexter T. K. Poon ◽  
Lori V. Coren ◽  
David E. Ott
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Class Ii ◽  
Hla Class Ii ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Protein Incorporation ◽  
Hiv 1

ABSTRACT HLA class II DR is one of the most abundant cell surface proteins incorporated onto human immunodeficiency virus type 1 (HIV-1) during budding. The mechanism for HLA class II protein incorporation is not known and may involve a viral protein. To determine whether Env affects HLA class II protein incorporation, HIV-1 virions, either with or without Env on their surface, were produced from HLA class II-expressing cells and analyzed by whole-virus immunoprecipitation with antisera against HLA class II proteins. HLA class II proteins were detected on virions only when wild-type Env was incorporated, while similar experiments showed that HLA class I proteins were incorporated independent of Env packaging. Therefore, the packaging of HIV-1 Env protein is required for the efficient incorporation of HLA class II but not class I proteins into the virion. Analysis of two Env mutants revealed that the presence of a 43-amino-acid sequence between amino acids 708 and 750 in the gp41TM cytoplasmic tail was required for efficient incorporation of HLA class II proteins. These data show that HIV-1 actively incorporates HLA class II proteins in a process that, either directly or indirectly, requires Env.

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