scholarly journals Construction of Soluble Mamu-B*1703, a Class I Major Histocompatibility Complex of Chinese Rhesus Macaques, Monomer and Tetramer Loaded with a Simian Immunodeficiency Virus Peptide

2009 ◽  
Vol 6 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Dongyun Ouyang ◽  
Xiaoying Wang ◽  
Xianhui He ◽  
Lihui Xu ◽  
Huanjing Shi ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Chinese Rhesus Macaques

scholarly journals Impact of Nef-Mediated Downregulation of Major Histocompatibility Complex Class I on Immune Response to Simian Immunodeficiency Virus

2004 ◽  
Vol 78 (23) ◽  
pp. 13335-13344 ◽  
Author(s):  
Tomek Swigut ◽  
Louis Alexander ◽  
Jennifer Morgan ◽  
Jeff Lifson ◽  
Keith G. Mansfield ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Cellular Response ◽  
Lymphocyte Activation ◽  
Class I ◽  
Wild Type Virus ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT Functional activities that have been ascribed to the nef gene product of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) include CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, downregulation of other plasma membrane proteins, and lymphocyte activation. Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities. Monkeys infected with these mutant forms of SIV exhibited higher levels of CD8+ T-cell responses 4 to 16 weeks postinfection than seen in monkeys infected with the parental wild-type virus. Furthermore, unusual compensatory mutations appeared by 16 to 32 weeks postinfection which restored some or all of the MHC-downregulating activity. These results indicate that nef does serve to limit the virus-specific CD8 cellular response of the host and that the ability to downregulate MHC class I contributes importantly to the totality of nef function.

scholarly journals Highly Pathogenic Simian Immunodeficiency Virus mne Variants That Emerge during the Course of Infection Evolve Enhanced Infectivity and the Ability To Downregulate CD4 but Not Class I Major Histocompatibility Complex Antigens

2002 ◽  
Vol 76 (13) ◽  
pp. 6425-6434 ◽  
Author(s):  
Parul G. Patel ◽  
Monica T. Yu Kimata ◽  
Julia E. Biggins ◽  
Joelle M. Wilson ◽  
Jason T. Kimata
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Highly Pathogenic ◽  
Pathogenic Variants ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT The replicative, cytopathic, and antigenic properties of simian immunodeficiency virus (SIV) variants influence its replication efficiency in vivo. To further define the viral properties and determinants that may be important for high-level replication in vivo and progression to AIDS, we compared a minimally pathogenic SIVmne molecular clone with two highly pathogenic variants cloned from late stages of infection. Both variants had evolved greater infectivity than the parental clone due to mutations in nef. Interestingly, a pol determinant in one of the highly pathogenic variants also contributed to its increased infectivity. Furthermore, because replication in vivo may also be influenced by the ability of a virus to evade the cellular immune response of the host, we examined whether the variants were more capable of downregulating surface expression of class I major histocompatibility complex (MHC). Decreased MHC class I expression was not observed in cells infected with any of the viruses. Furthermore, the Nef proteins of the highly pathogenic variants only slightly reduced surface MHC class I expression in transfected cells, although they efficiently downregulated CD4. Together, these data demonstrate that mutations which can enhance viral infectivity, as well as CD4 downregulation, may be important for efficient replication of SIV in the host. However, Nef-mediated reduction of MHC class I expression does not appear to be critical for the increased in vivo replicative ability of highly pathogenic late variants.

scholarly journals CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing

2001 ◽  
Vol 75 (2) ◽  
pp. 738-749 ◽  
Author(s):  
Todd M. Allen ◽  
Bianca R. Mothé ◽  
John Sidney ◽  
Peicheng Jing ◽  
John L. Dzuris ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Mononuclear Cells ◽  
Class I ◽  
Binding Motif ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Immunodeficiency Virus

ABSTRACT It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8+ response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8+ epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*012, a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparentKd values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01+ macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.

scholarly journals Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian–human immunodeficiency virus infection in macaques

2012 ◽  
Vol 93 (7) ◽  
pp. 1506-1518 ◽  
Author(s):  
Gui-Bo Yang ◽  
Yufei Wang ◽  
Kaboutar Babaahmady ◽  
Jørgen Schøller ◽  
Durdana Rahman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Major Histocompatibility Complex ◽  
Rhesus Macaques ◽  
Class I ◽  
Major Histocompatibility ◽  
Viral Loads ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Peak Viral Load ◽  
Hiv Gp120

Genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (MHC) is critical in controlling human immunodeficiency virus (HIV) infection. The objectives of this study were to determine whether novel recombinant Mamu MHC constructs would elicit protection against rectal challenge with heterologous simian–human immunodeficiency virus (SHIV) strain SF162.P4 in rhesus macaques. Mamu class I and II gene products were linked together with HIV gp140, simian immunodeficiency virus (SIV) p27 and heat-shock protein 70 to dextran. The vaccine was administered to two groups, each consisting of nine macaques, either subcutaneously (SC), or rectally and boosted by SC immunization. The controls were untreated or adjuvant-treated animals. Repetitive rectal challenges with up to ten doses of SHIV SF162.P4 showed a significant decrease in the peak and sequential viral RNA concentrations, and three macaques remained uninfected, in the nine SC-immunized animals, compared with infection in all nine controls. Macaques immunized rectally followed by SC boosters showed a less significant decrease in both sequential and peak viral loads compared with the SC-immunized animals, and all were infected following rectal challenge with SHIV SF162.P4. Plasma and mucosal IgG and IgA antibodies to Mamu class I alleles and HIV gp120, as well as to RANTES (regulated upon activation, normal T-cell expressed, and secreted; CCR5) were increased, and showed significant inverse correlations with the peak viral load. These results suggested that allo-immunization with recombinant MHC constructs linked to HIV–SIV antigens merits further investigation in preventing HIV-1 infection.

scholarly journals Efficient Class I Major Histocompatibility Complex Down-Regulation by Simian Immunodeficiency Virus Nef Is Associated with a Strong Selective Advantage in Infected Rhesus Macaques

2001 ◽  
Vol 75 (21) ◽  
pp. 10532-10536 ◽  
Author(s):  
Jan Münch ◽  
Nicole Stolte ◽  
Dietmar Fuchs ◽  
Christiane Stahl-Hennig ◽  
Frank Kirchhoff
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Rhesus Macaques ◽  
Selective Advantage ◽  
Class I ◽  
Down Regulation ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT Substitution of Y223F disrupts the ability of simian immunodeficiency virus (SIV) Nef to down-modulate major histocompatibility complex (MHC) class I from the cell surface but has no effect on other Nef functions, such as down-regulation of CD4, CD28, and CD3 cell surface expression or stimulation of viral replication and enhancement of virion infectivity. Inoculation of three rhesus macaques with the SIVmac239 Y223F-Nef variant revealed that this point mutation consistently reverts and that Nef activity in MHC class I down-modulation is fully restored within 4 weeks after infection. Our results demonstrate a strong selective pressure for a tyrosine at amino acid position 223 in SIV Nef, and they constitute evidence that Nef-mediated MHC class I down-regulation provides a selective advantage for viral replication in vivo.

scholarly journals The High-Frequency Major Histocompatibility Complex Class I Allele Mamu-B*17 Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 Replication

2006 ◽  
Vol 80 (10) ◽  
pp. 5074-5077 ◽  
Author(s):  
Levi J. Yant ◽  
Thomas C. Friedrich ◽  
Randall C. Johnson ◽  
Gemma E. May ◽  
Nicholas J. Maness ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Simian Immunodeficiency Virus ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Viral Control ◽  
Plasma Virus ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT Particular HLA alleles are associated with reduced human immunodeficiency virus replication. It has been difficult, however, to characterize the immune correlates of viral control. An analysis of the influence of major histocompatibility complex class I alleles on viral control in 181 simian immunodeficiency virus SIVmac239-infected rhesus macaques revealed that Mamu-B * 17 was associated with a 26-fold reduction in plasma virus concentrations (P < 0.001). Mamu-B * 17 was also enriched 1,000-fold in a group of animals that controlled viral replication. Even after accounting for this group, Mamu-B * 17 was associated with an eightfold reduction in plasma virus concentrations (P < 0.001). Mamu-B * 17-positive macaques could, therefore, facilitate our understanding of the correlates of viral control.

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