scholarly journals Roles of Target Cells and Virus-Specific Cellular Immunity in Primary Simian Immunodeficiency Virus Infection

2004 ◽  
Vol 78 (9) ◽  
pp. 4866-4875 ◽  
Author(s):  
Roland R. Regoes ◽  
Rustom Antia ◽  
David A. Garber ◽  
Guido Silvestri ◽  
Mark B. Feinberg ◽  
...  
Keyword(s):  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Cellular Immunity ◽  
Target Cell ◽  
Rhesus Macaques ◽  
Target Cells ◽  
Ongoing Debate ◽  
Data Set ◽  
Infection Period ◽  
Immunodeficiency Virus

ABSTRACT There is an ongoing debate on whether acute human immunodeficiency virus infection is controlled by target cell limitation or by virus-specific cellular immunity. To resolve this question, we developed a novel mathematical modeling scheme which allows us to incorporate measurements of virus load, target cells, and virus-specific immunity and applied it to a comprehensive data set generated in an experiment involving rhesus macaques infected with simian immunodeficiency virus. Half of the macaques studied were treated during the primary infection period with reagents which block T-cell costimulation and as a result displayed severely impaired virus-specific immune responses. Our results show that early viral replication in normal infection is controlled to a large extent by virus-specific CD8+ T cells and not by target cell limitation.

scholarly journals Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4+ T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication

2000 ◽  
Vol 74 (20) ◽  
pp. 9388-9395 ◽  
Author(s):  
Simoy Goldstein ◽  
Charles R. Brown ◽  
Houman Dehghani ◽  
Jeffrey D. Lifson ◽  
Vanessa M. Hirsch
Keyword(s):  
T Cell ◽  
Simian Immunodeficiency Virus ◽  
Rank Order ◽  
Rhesus Macaques ◽  
Target Cells ◽  
Plasma Viremia ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT Previous studies with simian immunodeficiency virus (SIV) infection of rhesus macaques suggested that the intrinsic susceptibility of peripheral blood mononuclear cells (PBMC) to infection with SIV in vitro was predictive of relative viremia after SIV challenge. The present study was conducted to evaluate this parameter in a well-characterized cohort of six rhesus macaques selected for marked differences in susceptibility to SIV infection in vitro. Rank order relative susceptibility of PBMC to SIVsmE543-3-infection in vitro was maintained over a 1-year period of evaluation. Differential susceptibility of different donors was maintained in CD8+T-cell-depleted PBMC, macrophages, and CD4+ T-cell lines derived by transformation of PBMC with herpesvirus saimiri, suggesting that this phenomenon is an intrinsic property of CD4+target cells. Following intravenous infection of these macaques with SIVsmE543-3, we observed a wide range in plasma viremia which followed the same rank order as the relative susceptibility established by in vitro studies. A significant correlation was observed between plasma viremia at 2 and 8 weeks postinoculation and in vitro susceptibility (P < 0.05). The observation that the two most susceptible macaques were seropositive for simian T-lymphotropic virus type 1 may suggests a role for this viral infection in enhancing susceptibility to SIV infection in vitro and in vivo. In summary, intrinsic susceptibility of CD4+ target cells appears to be an important factor influencing early virus replication patterns in vivo that should be considered in the design and interpretation of vaccine studies using the SIV/macaque model.

Administration of 9-[2-(Phosphonomethoxy)propyl] adenine (PMPA) for Prevention of Perinatal Simian Immunodeficiency Virus Infection in Rhesus Macaques

1998 ◽  
Vol 14 (9) ◽  
pp. 761-773 ◽  
Author(s):  
KOEN K.A. VAN ROMPAY ◽  
MARTA L. MARTHAS ◽  
JEFFREY D. LIFSON ◽  
CHRISTOPHER J. BERARDI ◽  
GABRIELA M. VASQUEZ ◽  
...  
Keyword(s):  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Simian Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus

scholarly journals Estimating the Effectiveness of Simian Immunodeficiency Virus-Specific CD8+ T Cells from the Dynamics of Viral Immune Escape

2007 ◽  
Vol 81 (21) ◽  
pp. 11982-11991 ◽  
Author(s):  
Judith N. Mandl ◽  
Roland R. Regoes ◽  
David A. Garber ◽  
Mark B. Feinberg
Keyword(s):  
T Cells ◽  
Simian Immunodeficiency Virus ◽  
Viral Escape ◽  
Target Cells ◽  
Data Set ◽  
Ctl Response ◽  
Specific Ctls ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT Antiviral CD8+ T cells are thought to play a significant role in limiting the viremia of human and simian immunodeficiency virus (HIV and SIV, respectively) infections. However, it has not been possible to measure the in vivo effectiveness of cytotoxic T cells (CTLs), and hence their contribution to the death rate of CD4+ T cells is unknown. Here, we estimated the ability of a prototypic antigen-specific CTL response against a well-characterized epitope to recognize and kill infected target cells by monitoring the immunodominant Mamu-A*01-restricted Tat SL8 epitope for escape from Tat-specific CTLs in SIVmac239-infected macaques. Fitting a mathematical model that incorporates the temporal kinetics of specific CTLs to the frequency of Tat SL8 escape mutants during acute SIV infection allowed us to estimate the in vivo killing rate constant per Tat SL8-specific CTL. Using this unique data set, we show that at least during acute SIV infection, certain antiviral CD8+ T cells can have a significant impact on shortening the longevity of infected CD4+ T cells and hence on suppressing virus replication. Unfortunately, due to viral escape from immune pressure and a dependency of the effectiveness of antiviral CD8+ T-cell responses on the availability of sufficient CD4+ T cells, the impressive early potency of the CTL response may wane in the transition to the chronic stage of the infection.

scholarly journals A Potent anti-Simian Immunodeficiency Virus Neutralizing Antibody Induction Associated with a Germline Immunoglobulin Gene Polymorphism in Rhesus Macaques

2021 ◽  
Author(s):  
Saori Matsuoka ◽  
Takeo Kuwata ◽  
Hiroshi Ishii ◽  
Tsuyoshi Sekizuka ◽  
Makoto Kuroda ◽  
...  
Keyword(s):  
Virus Infection ◽  
Gene Polymorphism ◽  
B Cell ◽  
Simian Immunodeficiency Virus ◽  
Germ Line ◽  
Rhesus Macaques ◽  
Immunodeficiency Virus ◽  
Antibody Induction ◽  
The Impact ◽  
Class Antibody

Virus infection induces B cells with a wide variety of B cell receptor (BCR) repertoires. Patterns of induced BCR repertoires are different in individuals, while the underlying mechanism causing this difference remains largely unclear. In particular, the impact of germ line BCR immunoglobulin (Ig) gene polymorphism on B cell/antibody induction has not fully been determined. In the present study, we found a potent antibody induction associated with a germ line BCR Ig gene polymorphism. B404-class antibodies, which were previously reported as potent anti-simian immunodeficiency virus (SIV) neutralizing antibodies using the germ line VH3.33 gene-derived Ig heavy chain, were induced in five of 10 rhesus macaques after SIVsmH635FC infection. Investigation of VH3.33 genes in B404-class antibody inducers (n = 5) and non-inducers (n = 5) revealed association of B404-class antibody induction with a germ line VH3.33 polymorphism. Analysis of reconstructed antibodies indicated that the VH3.33 residue 38 is the determinant for B404-class antibody induction. B404-class antibodies were induced in all the macaques possessing the B404-associated VH3.33 allele, even under undetectable viremia. Our results show that a single nucleotide polymorphism in germ line VH genes could be a determinant for induction of potent antibodies against virus infection, implying that germ line VH-gene polymorphisms can be a factor restricting effective antibody induction or responsiveness to vaccination. IMPORTANCE Vaccines against a wide variety of infectious diseases have been developed mostly to induce antibodies targeting pathogens. However, small but significant percentage of people fail to mount potent antibody responses after vaccination, while the underlying mechanism of host failure in antibody induction remains largely unclear. In particular, the impact of germ line B cell receptor (BCR)/antibody immunoglobulin (Ig) gene polymorphism on B cell/antibody induction has not fully been determined. In the present study, we found a potent anti-simian immunodeficiency virus neutralizing antibody induction associated with a germ line BCR/antibody Ig gene polymorphism in rhesus macaques. Our results demonstrate that a single nucleotide polymorphism in germ line Ig genes could be a determinant for induction of potent antibodies against virus infection, implying that germ line BCR/antibody Ig gene polymorphisms can be a factor restricting effective antibody induction or responsiveness to vaccination.

scholarly journals Role of IL-15 Signaling in the Pathogenesis of Simian Immunodeficiency Virus Infection in Rhesus Macaques

2019 ◽  
Vol 203 (11) ◽  
pp. 2928-2943
Author(s):  
Afam A. Okoye ◽  
Maren Q. DeGottardi ◽  
Yoshinori Fukazawa ◽  
Mukta Vaidya ◽  
Chike O. Abana ◽  
...  
Keyword(s):  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Simian Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus

scholarly journals Plasma Proteomic Analysis of Simian Immunodeficiency Virus Infection of Rhesus Macaques

2010 ◽  
Vol 9 (9) ◽  
pp. 4721-4731 ◽  
Author(s):  
Jayme L. Wiederin ◽  
Robert M. Donahoe ◽  
James R. Anderson ◽  
Fang Yu ◽  
Howard S. Fox ◽  
...  
Keyword(s):  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Proteomic Analysis ◽  
Rhesus Macaques ◽  
Simian Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus

scholarly journals Use of a Small Molecule CCR5 Inhibitor in Macaques to Treat Simian Immunodeficiency Virus Infection or Prevent Simian–Human Immunodeficiency Virus Infection

2003 ◽  
Vol 198 (10) ◽  
pp. 1551-1562 ◽  
Author(s):  
Ronald S. Veazey ◽  
Per Johan Klasse ◽  
Thomas J. Ketas ◽  
Jacqueline D. Reeves ◽  
Michael Piatak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Small Molecule ◽  
Rhesus Macaques ◽  
Sexual Transmission ◽  
Immunodeficiency Virus ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) fuses with cells after sequential interactions between its envelope glycoproteins, CD4 and a coreceptor, usually CC chemokine receptor 5 (CCR5) or CXC receptor 4 (CXCR4). CMPD 167 is a CCR5-specific small molecule with potent antiviral activity in vitro. We show that CMPD 167 caused a rapid and substantial (4–200-fold) decrease in plasma viremia in six rhesus macaques chronically infected with simian immunodeficiency virus (SIV) strains SIVmac251 or SIVB670, but not in an animal infected with the X4 simian–human immunodeficiency virus (SHIV), SHIV-89.6P. In three of the SIV-infected animals, viremia reduction was sustained. In one, there was a rapid, but partial, rebound and in another, there was a rapid and complete rebound. There was a substantial delay (&gt;21 d) between the end of therapy and the onset of full viremia rebound in two animals. We also evaluated whether vaginal administration of gel-formulated CMPD 167 could prevent vaginal transmission of the R5 virus, SHIV-162P4. Complete protection occurred in only 2 of 11 animals, but early viral replication was significantly less in the 11 CMPD 167-recipients than in 9 controls receiving carrier gel. These findings support the development of small molecule CCR5 inhibitors as antiviral therapies, and possibly as components of a topical microbicide to prevent HIV-1 sexual transmission.

scholarly journals Rhesus Macaque Polyclonal and Monoclonal Antibodies Inhibit Simian Immunodeficiency Virus in the Presence of Human or Autologous Rhesus Effector Cells

2006 ◽  
Vol 80 (18) ◽  
pp. 9217-9225 ◽  
Author(s):  
Donald N. Forthal ◽  
Gary Landucci ◽  
Kelly Stefano Cole ◽  
Marta Marthas ◽  
Juan C. Becerra ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Human Peripheral Blood ◽  
Rhesus Macaques ◽  
Biological Activities ◽  
Fc Receptor ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells ◽  
Virus Inhibition ◽  
Immunodeficiency Virus

ABSTRACT Although antibodies can prevent or modulate lentivirus infections in nonhuman primates, the biological functions of antibody responsible for such effects are not known. We sought to determine the role of antibody-dependent cell-mediated virus inhibition (ADCVI), an antibody function that inhibits virus yield from infected cells in the presence of Fc receptor-bearing effector cells, in preventing or controlling SIVmac251 infection in rhesus macaques (Macaca mulatta). Using CEMx174 cells infected with simian immunodeficiency virus mac251 (SIVmac251), both polyclonal and monoclonal anti-SIV antibodies were capable of potent virus inhibition in the presence of human peripheral blood mononuclear cell (PBMC) effector cells. In the absence of effector cells, virus inhibition was generally very poor. PBMCs from healthy rhesus macaques were also capable of mediating virus inhibition either against SIVmac251-infected CEMx174 cells or against infected, autologous rhesus target cells. We identified both CD14+ cells and, to a lesser extent, CD8+ cells as the effector cell population in the rhesus PBMCs. Finally, pooled, nonneutralizing SIV-antibody-positive serum, shown in a previous study to prevent infection of neonatal macaques after oral SIVmac251 challenge, had potent virus-inhibitory activity in the presence of effector cells; intact immunoglobulin G, rather than F(ab′)2, was required for such activity. This is the first demonstration of both humoral and cellular ADCVI functions in the macaque-SIV model. ADCVI activity in nonneutralizing serum that prevents SIV infection suggests that ADCVI may be a protective immune function. Finally, our data underscore the potential importance of Fc-Fc receptor interactions in mediating biological activities of antibody.

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