Expression of the Human Immunodeficiency Virus-Tat Gene in Lymphoid Tissues of Transgenic Mice Is Associated With B-Cell Lymphoma

Blood ◽  
1999 ◽  
Vol 94 (1) ◽  
pp. 275-282 ◽  
Author(s):  
Ramendra K. Kundu ◽  
Frank Sangiorgi ◽  
Lan-Ying Wu ◽  
Paul K. Pattengale ◽  
David R. Hinton ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transgenic Mice ◽  
B Cell ◽  
Cultured Cells ◽  
B Cell Lymphoma ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Genetic Event ◽  
Immunodeficiency Virus ◽  
Hiv 1

The human immunodeficiency virus type 1 (HIV-1) Tat gene, a potent transactivator of viral and cellular genes, has been proposed as a key agent in the pathogenesis of acquired immune deficiency syndrome related disorders, including nonHodgkin’s lymphoma. In cultured cells, the HIV-1 Tat protein can induce the expression of the cytokines interleukin-6 (IL-6) and IL-10, which are known to induce proliferation and differentiation of lymphoid cells. Such alterations in cytokine expression, together with a secondary genetic event, are thought to ultimately lead to oncogenic transformation. To address the influence of Tat on lymphoid development in the context of the whole organism, we produced several transgenic mouse lines that express the Tat gene under the control of an actin promoter. We show here that this promoter directs expression to a variety of sites, including spleen, bone marrow, and lymph nodes. Approximately 25% to 30% of the Tat-transgenic population developed enlarged spleens within 1 year after birth. On histological examination, a significant number of spleens from Tat-transgenic mice exhibited malignant lymphoma of B-cell origin. IgG heavy chain rearrangement confirmed the clonal B-cell nature of these lymphoproliferations. In contrast, T-cell receptor genes exhibited a germline (unrearranged) structure. Reverse transcription polymerase chain reaction analysis of transgenic spleens revealed that mRNA encoding cytokines IL-6 and IL-10 was upregulated, suggesting a possible mechanism for the B-cell expansion in vivo.

scholarly journals Human Immunodeficiency Virus Type 1 Bound to B Cells: Relationship to Virus Replicating in CD4+ T Cells and Circulating in Plasma

2002 ◽  
Vol 76 (17) ◽  
pp. 8855-8863 ◽  
Author(s):  
Angela Malaspina ◽  
Susan Moir ◽  
David C. Nickle ◽  
Eileen T. Donoghue ◽  
Kisani M. Ogwaro ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Peripheral Blood ◽  
Lymphoid Tissues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) virions bind to B cells in the peripheral blood and lymph nodes through interactions between CD21 on B cells and complement-complexed virions. B-cell-bound virions have been shown to be highly infectious, suggesting a unique mode of HIV-1 dissemination by B cells circulating between peripheral blood and lymphoid tissues. In order to investigate the relationship between B-cell-bound HIV-1 and viruses found in CD4+ T cells and in plasma, we examined the genetic relationships of HIV-1 found in the blood and lymph nodes of chronically infected patients with heteroduplex mobility and tracking assays and DNA sequence analysis. In samples from 13 of 15 patients examined, HIV-1 variants in peripheral blood-derived B cells were closely related to virus in CD4+ T cells and more divergent from virus in plasma. In samples from five chronically viremic patients for whom analyses were extended to include lymph node-derived HIV-1 isolates, B-cell-associated HIV-1 and CD4+-T-cell-associated HIV-1 in the lymph nodes were equivalent in their divergence from virus in peripheral blood-derived B cells and generally more distantly related to virus in peripheral blood-derived CD4+ T cells. These results indicates virologic cross talk between B cells and CD4+ T cells within the microenvironment of lymphoid tissues and, to a lesser extent, between cells in lymph nodes and the peripheral blood. These findings also indicate that most of the virus in plasma originates from cells other than CD4+ T cells in the peripheral blood and lymph nodes.

scholarly journals Early Detection of Human Immunodeficiency Virus Type 1-Specific B-Lymphocyte-Derived Antibodies in a High-Risk Population

2009 ◽  
Vol 16 (7) ◽  
pp. 1060-1065 ◽  
Author(s):  
Odd Odinsen ◽  
David Parker ◽  
Frans Radebe ◽  
Mikey Guness ◽  
David A Lewis
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
B Cell ◽  
Immunodeficiency Virus ◽  
Hiv Antibodies ◽  
P24 Antigen ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT Diagnosis of acute human immunodeficiency virus (HIV) infection, a key driver of the HIV epidemic, remains a public health challenge. The PlasmAcute technology offers an opportunity to detect early anti-HIV antibody responses. B lymphocytes (B cells) were isolated from the blood of seronegative miners in South Africa by using the PlasmAcute method. B-cell lysates and paired sera were tested for anti-HIV-1 antibodies by two different enzyme-linked immunosorbent assays; immunoreactivity was confirmed by Western blotting. All volunteers were tested for HIV type 1 (HIV-1) viral load, p24 antigen, and CD4 count. Sera from HIV-seronegative men who had positive viral loads and were positive for p24 antigen were retested for anti-HIV antibodies after immune complex dissociation. Anti-HIV antibodies were detected in lysates from 16/259 subjects without immunoreactivity in paired sera. Four subjects, one of whom had a positive viral load initially, subsequently seroconverted. Six subjects showed transient anti-HIV-1 antibodies in the lysates and tested negative for all markers at the follow-up. Five subjects without follow-up data initially had lysate-positive/serum-negative samples, and these cases were classified as inconclusive. One subject had lysate antibodies and a detectable viral load but was seronegative at follow-up. In conclusion, lysate-derived anti-HIV-1 B-cell antibodies can be detected prior to seroconversion and earlier than or contemporary with HIV-1 RNA detection.

scholarly journals Characterization of Simian Immunodeficiency Virus SIVSM/Human Immunodeficiency Virus Type 2 Vpx Function in Human Myeloid Cells

2008 ◽  
Vol 82 (24) ◽  
pp. 12335-12345 ◽  
Author(s):  
Caroline Goujon ◽  
Vanessa Arfi ◽  
Thomas Pertel ◽  
Jeremy Luban ◽  
Julia Lienard ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Intracellular Localization ◽  
Lymphoid Cells ◽  
Viral Dna ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 2 (HIV-2)/simian immunodeficiency virus SIVSM Vpx is incorporated into virion particles and is thus present during the early steps of infection, when it has been reported to influence the nuclear import of viral DNA. We recently reported that Vpx promoted the accumulation of full-length viral DNA following the infection of human monocyte-derived dendritic cells (DCs). This positive effect was exerted following the infection of DCs with cognate viruses and with retroviruses as divergent as HIV-1, feline immunodeficiency virus, and even murine leukemia virus, leading us to suggest that Vpx counteracted an antiviral restriction present in DCs. Here, we show that Vpx is required, albeit to a different extent, for the infection of all myeloid but not of lymphoid cells, including monocytes, macrophages, and monocytoid THP-1 cells that had been induced to differentiate with phorbol esters. The intracellular localization of Vpx was highly heterogeneous and cell type dependent, since Vpx localized differently in HeLa cells and DCs. Despite these differences, no clear correlation between the functionality of Vpx and its intracellular localization could be drawn. As a first insight into its function, we determined that SIVSM/HIV-2 and SIVRCM Vpx proteins interact with the DCAF1 adaptor of the Cul4-based E3 ubiquitin ligase complex recently described to associate with HIV-1 Vpr and HIV-2 Vpx. However, the functionality of Vpx proteins in the infection of DCs did not strictly correlate with DCAF1 binding, and knockdown experiments failed to reveal a functional role for this association in differentiated THP-1 cells. Lastly, when transferred in the context of a replication-competent viral clone, Vpx was required for replication in DCs.

scholarly journals Acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human immunodeficiency virus type 1-associated T-cell transformation

Blood ◽  
1992 ◽  
Vol 79 (7) ◽  
pp. 1768-1774 ◽  
Author(s):  
BG Herndier ◽  
BT Shiramizu ◽  
NE Jewett ◽  
KD Aldape ◽  
GR Reyes ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
B Cell ◽  
Virus Type ◽  
Cell Lymphoma ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Abstract The majority of lymphomas in the setting of acquired, iatrogenic, or congenital immunodeficiencies are B-cell lymphoproliferations. We describe a rare T-cell lymphoma in a fulminantly ill patient infected with human immunodeficiency virus type 1 (HIV-1). The T-cell nature of the process was defined genotypically (monoclonal T-cell receptor beta- chain [CT beta] rearrangement) and phenotypically (CD45RO+, CD4+, CD5+, CD25+, CD8-, CD3- and negative for a variety of B-cell and monocyte markers). The CD4+, CD25+ (interleukin-2 receptor [IL-2R]) phenotype with production of IL-2 and IL-2R RNA is analogous to human T- lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATLL); however, no HTLV-1 could be detected. Southern blot analysis did demonstrate monoclonally integrated HIV-1 within the tumor genome. Furthermore, the tumor cells were producing HIV p24 antigen as shown by immunohistochemistry. This is the first case of acquired immunodeficiency syndrome (AIDS)-associated non- Hodgkin's lymphoma in which HIV-1 infection may have played a central role in the lymphocyte transformation process.

scholarly journals Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia

2008 ◽  
Vol 82 (24) ◽  
pp. 12449-12463 ◽  
Author(s):  
Georgia D. Tomaras ◽  
Nicole L. Yates ◽  
Pinghuang Liu ◽  
Li Qin ◽  
Genevieve G. Fouda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
B Cell ◽  
Human Immunodeficiency Virus Type ◽  
Igg Antibodies ◽  
Plasma Virus ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.

scholarly journals Human Immunodeficiency Virus Type 1-Associated CD40 Ligand Transactivates B Lymphocytes and Promotes Infection of CD4+ T Cells

2007 ◽  
Vol 81 (11) ◽  
pp. 5872-5881 ◽  
Author(s):  
Geneviève Martin ◽  
Jocelyn Roy ◽  
Corinne Barat ◽  
Michel Ouellet ◽  
Caroline Gilbert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
B Cell ◽  
B Lymphocytes ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nuclear Translocation ◽  
Cd40 Ligand ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Abnormal activation of B lymphocytes is a feature commonly seen in human immunodeficiency virus type 1 (HIV-1)-infected persons. However, the mechanism(s) responsible for this dysfunction is still poorly understood. Having recently shown that CD40L, the ligand for CD40, is inserted within emerging HIV-1 particles, we hypothesized that the contact between virus-anchored host CD40L and CD40 on the surface of B lymphocytes might result in the activation of this cell type. We report here that CD40L-bearing viruses, but not isogenic virions lacking host-derived CD40L, can induce immunoglobulin G and interleukin-6 production. Furthermore, such viral entities were found to induce B-cell homotypic adhesion. These effects were paralleled at the intracellular level by the nuclear translocation of the ubiquitous transcription factor NF-κB. The presence of host-derived CD40L within virions resulted in an increased virus attachment to B cells and a more-efficient B-cell-mediated transfer of HIV-1 to autologous CD4+ T lymphocytes. All the above processes were independent of the virus-encoded envelope glycoproteins. Altogether, the data gathered from this series of investigations suggest that the incorporation of host-encoded CD40L in HIV-1 is likely to play a role in the B-cell abnormalities that are seen in infected individuals.

scholarly journals Acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human immunodeficiency virus type 1-associated T-cell transformation

Blood ◽  
1992 ◽  
Vol 79 (7) ◽  
pp. 1768-1774 ◽  
Author(s):  
BG Herndier ◽  
BT Shiramizu ◽  
NE Jewett ◽  
KD Aldape ◽  
GR Reyes ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
B Cell ◽  
Virus Type ◽  
Cell Lymphoma ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

The majority of lymphomas in the setting of acquired, iatrogenic, or congenital immunodeficiencies are B-cell lymphoproliferations. We describe a rare T-cell lymphoma in a fulminantly ill patient infected with human immunodeficiency virus type 1 (HIV-1). The T-cell nature of the process was defined genotypically (monoclonal T-cell receptor beta- chain [CT beta] rearrangement) and phenotypically (CD45RO+, CD4+, CD5+, CD25+, CD8-, CD3- and negative for a variety of B-cell and monocyte markers). The CD4+, CD25+ (interleukin-2 receptor [IL-2R]) phenotype with production of IL-2 and IL-2R RNA is analogous to human T- lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATLL); however, no HTLV-1 could be detected. Southern blot analysis did demonstrate monoclonally integrated HIV-1 within the tumor genome. Furthermore, the tumor cells were producing HIV p24 antigen as shown by immunohistochemistry. This is the first case of acquired immunodeficiency syndrome (AIDS)-associated non- Hodgkin's lymphoma in which HIV-1 infection may have played a central role in the lymphocyte transformation process.

Sign in / Sign up

Export Citation Format

Share Document