scholarly journals Apoptosis Correlates with Immune Activation in Intestinal Lymphoid Tissue from Macaques Acutely Infected by a Highly Enteropathic Simian Immunodeficiency Virus, SIVsmmPBj14

Virology ◽  
1996 ◽  
Vol 225 (1) ◽  
pp. 21-32 ◽  
Author(s):  
Suryaram Gummuluru ◽  
Francis J. Novembre ◽  
Mark Lewis ◽  
Harris A. Gelbard ◽  
Stephen Dewhurst
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Immune Activation ◽  
Lymphoid Tissue ◽  
Immunodeficiency Virus ◽  
Intestinal Lymphoid Tissue

scholarly journals Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection

2014 ◽  
Vol 20 (12) ◽  
pp. 1397-1400 ◽  
Author(s):  
Siddappa N Byrareddy ◽  
Brianne Kallam ◽  
James Arthos ◽  
Claudia Cicala ◽  
Fatima Nawaz ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Lymphoid Tissue ◽  
Mucosal Transmission ◽  
Immunodeficiency Virus

scholarly journals Loss of a Tyrosine-Dependent Trafficking Motif in the Simian Immunodeficiency Virus Envelope Cytoplasmic Tail Spares Mucosal CD4 Cells but Does Not Prevent Disease Progression

2012 ◽  
Vol 87 (3) ◽  
pp. 1528-1543 ◽  
Author(s):  
Matthew W. Breed ◽  
Andrea P. O. Jordan ◽  
Pyone P. Aye ◽  
Cornelis F. Lichtveld ◽  
Cecily C. Midkiff ◽  
...  
Keyword(s):  
T Cells ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Lamina Propria ◽  
T Cell Activation ◽  
Immune Activation ◽  
Cell Activation ◽  
Cytoplasmic Tail ◽  
Microbial Translocation ◽  
Immunodeficiency Virus

ABSTRACTA hallmark of pathogenic simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) infections is the rapid and near-complete depletion of mucosal CD4+T lymphocytes from the gastrointestinal tract. Loss of these cells and disruption of epithelial barrier function are associated with microbial translocation, which has been proposed to drive chronic systemic immune activation and disease progression. Here, we evaluate in rhesus macaques a novel attenuated variant of pathogenic SIVmac239, termed ΔGY, which contains a deletion of a Tyr and a proximal Gly from a highly conserved YxxØ trafficking motif in the envelope cytoplasmic tail. Compared to SIVmac239, ΔGY established a comparable acute peak of viremia but only transiently infected lamina propria and caused little or no acute depletion of mucosal CD4+T cells and no detectable microbial translocation. Nonetheless, these animals developed T-cell activation and declining peripheral blood CD4+T cells and ultimately progressed with clinical or pathological features of AIDS. ΔGY-infected animals also showed no infection of macrophages or central nervous system tissues even in late-stage disease. Although the ΔGY mutation persisted, novel mutations evolved, including the formation of new YxxØ motifs in two of four animals. These findings indicate that disruption of this trafficking motif by the ΔGY mutation leads to a striking alteration in anatomic distribution of virus with sparing of lamina propria and a lack of microbial translocation. Because these animals exhibited wild-type levels of acute viremia and immune activation, our findings indicate that these pathological events are dissociable and that immune activation unrelated to gut damage can be sufficient for the development of AIDS.

scholarly journals CD8+ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

2005 ◽  
Vol 79 (19) ◽  
pp. 12264-12272 ◽  
Author(s):  
Richard Stebbings ◽  
Neil Berry ◽  
Herman Waldmann ◽  
Pru Bird ◽  
Geoff Hale ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
T Lymphocyte ◽  
Lymphoid Tissue ◽  
Human Immunoglobulin ◽  
Wild Type ◽  
Lymphocyte Depletion ◽  
Immunodeficiency Virus

ABSTRACT In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.

scholarly journals Development of Neurological Disease Is Associated with Increased Immune Activation in Simian Immunodeficiency Virus-Infected Macaques

2012 ◽  
Vol 86 (24) ◽  
pp. 13795-13799 ◽  
Author(s):  
Q. Dang ◽  
S. Whitted ◽  
R. M. Goeken ◽  
J. M. Brenchley ◽  
K. Matsuda ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Immune Activation ◽  
Neurological Disease ◽  
Immunodeficiency Virus

scholarly journals Derivation and Characterization of Pathogenic Transmitted/Founder Molecular Clones from Simian Immunodeficiency Virus SIVsmE660 and SIVmac251 following Mucosal Infection

2016 ◽  
Vol 90 (19) ◽  
pp. 8435-8453 ◽  
Author(s):  
Michael J. Lopker ◽  
Gregory Q. Del Prete ◽  
Jacob D. Estes ◽  
Hui Li ◽  
Carolyn Reid ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Nonhuman Primate ◽  
Tissue Damage ◽  
Lymphoid Tissue ◽  
Chronic Infection ◽  
Rhesus Macaques ◽  
Clinical Endpoints ◽  
Immunodeficiency Virus ◽  
Infectious Molecular Clones ◽  
Virus Strains

ABSTRACTCurrently available simian immunodeficiency virus (SIV) infectious molecular clones (IMCs) and isolates used in nonhuman primate (NHP) models of AIDS were originally derived from infected macaques during chronic infection or end stage disease and may not authentically recapitulate features of transmitted/founder (T/F) genomes that are of particular interest in transmission, pathogenesis, prevention, and treatment studies. We therefore generated and characterized T/F IMCs from genetically and biologically heterogeneous challenge stocks of SIVmac251 and SIVsmE660. Single-genome amplification (SGA) was used to identify full-length T/F genomes present in plasma during acute infection resulting from atraumatic rectal inoculation of Indian rhesus macaques with low doses of SIVmac251 or SIVsmE660. All 8 T/F clones yielded viruses that were infectious and replication competentin vitro, with replication kinetics similar to those of the widely used chronic-infection-derived IMCs SIVmac239 and SIVsmE543. Phenotypically, the new T/F virus strains exhibited a range of neutralization sensitivity profiles. Four T/F virus strains were inoculated into rhesus macaques, and each exhibited typical SIV replication kinetics. The SIVsm T/F viruses were sensitive to TRIM5α restriction. All T/F viruses were pathogenic in rhesus macaques, resulting in progressive CD4+T cell loss in gastrointestinal tissues, peripheral blood, and lymphatic tissues. The animals developed pathological immune activation; lymphoid tissue damage, including fibrosis; and clinically significant immunodeficiency leading to AIDS-defining clinical endpoints. These T/F clones represent a new molecular platform for the analysis of virus transmission and immunopathogenesis and for the generation of novel “bar-coded” challenge viruses and next-generation simian-human immunodeficiency viruses that may advance the HIV/AIDS vaccine agenda.IMPORTANCENonhuman primate research has relied on only a few infectious molecular clones for a myriad of diverse research projects, including pathogenesis, preclinical vaccine evaluations, transmission, and host-versus-pathogen interactions. With new data suggesting a selected phenotype of the virus that causes infection (i.e., the transmitted/founder virus), we sought to generate and characterize infectious molecular clones from two widely used simian immunodeficiency virus lineages (SIVmac251 and SIVsmE660). Although the exact requirements necessary to be a T/F virus are not yet fully understood, we generated cloned viruses with all the necessary characteristic of a successful T/F virus. The cloned viruses revealed typical acute and set point viral-load dynamics with pathological immune activation, lymphoid tissue damage progressing to significant immunodeficiency, and AIDS-defining clinical endpoints in some animals. These T/F clones represent a new molecular platform for studies requiring authentic T/F viruses.

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