T cells expressing high levels of non-major histocompatibility complex (MHC)-restricted cytotoxicity are present in early and late clinical phases of human immunodeficiency virus 1 (HIV-1) infection

1989 ◽  
Vol 9 (2) ◽  
pp. 97-102 ◽  
Author(s):  
J. E. Morgan ◽  
C. B. Daul ◽  
R. D. de Shazo ◽  
W. A. Andes ◽  
N. H. Hyslop
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

scholarly journals Simian and Human Immunodeficiency Virus Nef Proteins Use Different Surfaces To Downregulate Class I Major Histocompatibility Complex Antigen Expression

2000 ◽  
Vol 74 (12) ◽  
pp. 5691-5701 ◽  
Author(s):  
Tomek Swigut ◽  
A. John Iafrate ◽  
Jan Muench ◽  
Frank Kirchhoff ◽  
Jacek Skowronski
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Class I ◽  
Detectable Effect ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) Nef proteins are related regulatory proteins that share several functions, including the ability to downregulate class I major histocompatibility complex (MHC) and CD4 expression on the cell surface and to alter T-cell-receptor-initiated signal transduction in T cells. We compared the mechanisms used by SIV mac239 Nef and HIV-1 Nef to downregulate class I MHC and found that the ability of SIV Nef to downregulate class I MHC requires a unique C-terminal region of the SIV mac239 Nef molecule which is not found in HIV-1 Nef. Interestingly, mutation of the PxxP motif in SIV Nef, unlike in HIV-1 Nef, does not affect class I MHC downregulation. We also found that downregulation of class I MHC by SIV Nef requires a conserved tyrosine in the cytoplasmic domain of the class I MHC heavy chain and involves accelerated endocytosis of class I complexes, as previously found with HIV-1 Nef. Thus, while SIV and HIV-1 Nef proteins use a similar mechanism to downregulate class I MHC expression, they have evolved different surfaces for molecular interactions with cell factors that regulate class I MHC traffic. Mutations in the C-terminal domain of SIV mac239 Nef selectively disrupt class I MHC downregulation, having no detectable effect on other functions of Nef, such as the downregulation of CD4 and CD3 surface expression, the stimulation of SIV virion infectivity, and the induction of SIV replication from T cells infected in the absence of stimulation. The resulting mutants will be useful reagents for studying the importance of class I MHC downregulation for SIV replication and AIDS pathogenesis in infected rhesus macaques.

scholarly journals Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules.

1992 ◽  
Vol 175 (6) ◽  
pp. 1417-1422 ◽  
Author(s):  
S Kozlowski ◽  
M Corr ◽  
T Takeshita ◽  
L F Boyd ◽  
C D Pendleton ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Class I ◽  
Converting Enzyme ◽  
Major Histocompatibility ◽  
Free System ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1

T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin-1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design.

scholarly journals CD8+ and CD20+ Lymphocytes Cooperate To Control Acute Simian Immunodeficiency Virus/Human Immunodeficiency Virus Chimeric Virus Infections in Rhesus Monkeys: Modulation by Major Histocompatibility Complex Genotype

2005 ◽  
Vol 79 (23) ◽  
pp. 14887-14898 ◽  
Author(s):  
Hanwen Mao ◽  
Bernard A. P. Lafont ◽  
Tatsuhiko Igarashi ◽  
Yoshiaki Nishimura ◽  
Charlie Brown ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Monkeys ◽  
Acute Infection ◽  
Major Histocompatibility ◽  
Highly Pathogenic ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT We have previously described two isogenic molecularly cloned simian immunodeficiency virus/human immunodeficiency virus chimeric viruses (SHIVs) that differ from one another by 9 amino acids and direct distinct clinical outcomes in inoculated rhesus monkeys. SHIVDH12R-Clone 7, like other highly pathogenic CXCR4-tropic SHIVs, induces rapid and complete depletions of CD4+ T lymphocytes and immunodeficiency in infected animals. In contrast, macaques inoculated with SHIVDH12R-Clone 8 experience only partial and transient losses of CD4+ T cells, show prompt control of their viremia, and remain healthy for periods of time extending for up to 4 years. The contributions of CD8+ and CD20+ lymphocytes in suppressing the replication of the attenuated SHIVDH12R-Clone 8 and maintaining a prolonged asymptomatic clinical course was assessed by treating animals with monoclonal antibodies that deplete each lymphocyte subset at the time of virus inoculation. The absence of either CD8+ or CD20+ cells during the SHIVDH12R-Clone 8 acute infection resulted in the rapid, complete, and irreversible loss of CD4+ T cells; sustained high levels of postpeak plasma viremia; and symptomatic disease in Mamu-A*01-negative Indian rhesus monkeys. In Mamu-A*01-positive animals, however, the aggressive, highly pathogenic phenotype was observed only in macaques depleted of CD8+ cells; SHIVDH12R-Clone 8 was effectively controlled in Mamu-A*01-positive monkeys in the absence of B lymphocytes. Taken together, these results indicate that both CD8+ and CD20+ B cells contribute to the control of primate lentiviral infection in Mamu-A*01-negative macaques. Furthermore, the major histocompatibility complex genotype of an infected animal, as exemplified by the Mamu-A*01 allele in this study, has the additional capacity to shift the balance of the composite immune response.

scholarly journals Characterization of a Major Histocompatibility Complex Class II X-Box-Binding Protein Enhancing Tat-Induced Transcription Directed by the Human Immunodeficiency Virus Type 1 Long Terminal Repeat

2000 ◽  
Vol 74 (19) ◽  
pp. 8989-9001 ◽  
Author(s):  
Carlo Mischiati ◽  
Giordana Feriotto ◽  
Monica Borgatti ◽  
Patrizio Giacomini ◽  
Roberto Gambari
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcription Factors ◽  
Major Histocompatibility Complex ◽  
Class Ii ◽  
The Other ◽  
Nuclear Proteins ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The X-box element present within the promoter region of genes belonging to the major histocompatibility complex (MHC) plays a pivotal role in the expression of class II molecules, since it contains the binding sites for several well-characterized transcription factors. We have analyzed a randomly selected compilation of viral genomes for the presence of elements homologous to the X box of the HLA-DRA gene. We found that human immunodeficiency virus type 1 (HIV-1) shows the highest frequency of X-like box elements per 1,000 bases of genome. Within the HIV-1 genome, we found an X-like motif in the TAR region of the HIV-1 long terminal repeat (LTR), a regulative region playing a pivotal role in Tat-induced HIV-1 transcription. The use of a decoy approach for nuclear proteins binding to this element, namely, XMAS (X-like motif activator sequence), performed by transfection of multiple copies of this sequence into cells carrying an integrated LTR-chloramphenicol acetyltransferase construct, suggests that this element binds to nuclear proteins that enhance Tat-induced transcription. In this report we have characterized two proteins, one binding to the XMAS motif and the other to the flanking regions of XMAS. Mobility shift assays performed on crude nuclear extracts or enriched fractions suggest that similar proteins bind to XMAS from HIV-1 and the X box of the HLA-DRA gene. Furthermore, a UV cross-linking assay suggests that one protein of 47 kDa, termed FAX (factor associated with XMAS)-1, binds to the XMAS of HIV-1. The other protein of 56 kDa was termed FAX-2. In a decoy ex vivo experiment, it was found that sequences recognizing both proteins are required to inhibit Tat-induced HIV-1 LTR-driven transcription. Taken together, the data reported in this paper suggest that XMAS and nearby sequences modulate Tat-induced HIV-1 transcription by binding to the X-box-binding proteins FAX-1 and FAX-2. The sequence homology between XMAS and X box is reflected in binding of a common protein, FAX-1, and similar functional roles in gene expression. To our knowledge, this is the first report showing that transcription factors binding to the X box of the MHC class II genes enhance the transcription of HIV-1.

scholarly journals Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1.

1994 ◽  
Vol 179 (2) ◽  
pp. 513-522 ◽  
Author(s):  
T R Kollmann ◽  
M Pettoello-Mantovani ◽  
X Zhuang ◽  
A Kim ◽  
M Hachamovitch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Human T Cells ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

A small animal model that could be infected with human immunodeficiency virus 1 (HIV-1) after peripheral inoculation would greatly facilitate the study of the pathophysiology of acute HIV-1 infection. The utility of SCID mice implanted with human fetal thymus and liver (SCID-hu mice) for studying peripheral HIV-1 infection in vivo has been hampered by the requirement for direct intraimplant injection of HIV-1 and the continued restriction of the resultant HIV-1 infection to the human thymus and liver (hu-thy/liv) implant. This may have been due to the very low numbers of human T cells present in the SCID-hu mouse peripheral lymphoid compartment. Since the degree of the peripheral reconstitution of SCID-hu mice with human T cells may be a function of the hu-thy/liv implant size, we increased the quantity of hu-thy/liv tissue implanted under the renal capsule and implanted hu-thy/liv tissue under the capsules of both kidneys. This resulted in SCID-hu mice in which significant numbers of human T cells were detected in the peripheral blood, spleens, and lymph nodes. After intraimplant injection of HIV-1 into these modified SCID-hu mice, significant HIV-1 infection was detected by quantitative coculture not only in the hu-thy/liv implant, but also in the spleen and peripheral blood. This indicated that HIV-1 infection can spread from the thymus to the peripheral lymphoid compartment. More importantly, a similar degree of infection of the hu-thy/liv implant and peripheral lymphoid compartment occurred after peripheral intraperitoneal inoculation with HIV-1. Active viral replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag RNA, and spliced tat/rev RNA in the hu-thy/liv implants, peripheral blood mononuclear cells (PBMC), spleens, and lymph nodes of these HIV-1-infected SCID-hu mice. As a first step in using our modified SCID-hu mouse model to investigate the pathophysiological consequences of HIV-1 infection, the effect of HIV-1 infection on the expression of human cytokines shown to enhance HIV-1 replication was examined. Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for human tumor necrosis factors alpha and beta, and interleukin 2 in their spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This suggested that HIV-1 infection in vivo can stimulate the expression of cytokine mRNA by human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Differential Incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and Major Histocompatibility Complex Class I and II Molecules into Human Immunodeficiency Virus Type 1 Virions and Microvesicles: Implications for Viral Pathogenesis and Immune Regulation

2001 ◽  
Vol 75 (13) ◽  
pp. 6173-6182 ◽  
Author(s):  
Mark T. Esser ◽  
David R. Graham ◽  
Lori V. Coren ◽  
Charles M. Trubey ◽  
Julian W. Bess ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Hiv Infection ◽  
Host Cell ◽  
Mhc Ii ◽  
Host Cell Proteins ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus (HIV) infection results in a functional impairment of CD4+ T cells long before a quantitative decline in circulating CD4+ T cells is evident. The mechanism(s) responsible for this functional unresponsiveness and eventual depletion of CD4+ T cells remains unclear. Both direct effects of cytopathic infection of CD4+ cells and indirect effects in which uninfected “bystander” cells are functionally compromised or killed have been implicated as contributing to the immunopathogenesis of HIV infection. Because T-cell receptor engagement of major histocompatibility complex (MHC) molecules in the absence of costimulation mediated via CD28 binding to CD80 (B7-1) or CD86 (B7-2) can lead to anergy or apoptosis, we determined whether HIV type 1 (HIV-1) virions incorporated MHC class I (MHC-I), MHC-II, CD80, or CD86. Microvesicles produced from matched uninfected cells were also evaluated. HIV infection increased MHC-II expression on T- and B-cell lines, macrophages, and peripheral blood mononclear cells (PBMC) but did not significantly alter the expression of CD80 or CD86. HIV virions derived from all MHC-II-positive cell types incorporated high levels of MHC-II, and both virions and microvesicles preferentially incorporated CD86 compared to CD80. CD45, expressed at high levels on cells, was identified as a protein present at high levels on microvesicles but was not detected on HIV-1 virions. Virion-associated, host cell-derived molecules impacted the ability of noninfectious HIV virions to trigger death in freshly isolated PBMC. These results demonstrate the preferential incorporation or exclusion of host cell proteins by budding HIV-1 virions and suggest that host cell proteins present on HIV-1 virions may contribute to the overall pathogenesis of HIV-1 infection.

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