Lentiviral latency in peripheral CD4+ T cells isolated from feline immunodeficiency virus-infected cats during the asymptomatic phase is not associated with hypermethylation of the proviral promoter

2012 ◽  
Vol 169 (1) ◽  
pp. 117-126 ◽  
Author(s):  
B. Murphy ◽  
C. Hillman ◽  
M. Mok ◽  
N. Vapniarsky
Blood ◽  
2003 ◽  
Vol 101 (4) ◽  
pp. 1213-1219 ◽  
Author(s):  
Sieghart Sopper ◽  
Dagmar Nierwetberg ◽  
Astrid Halbach ◽  
Ursula Sauer ◽  
Carsten Scheller ◽  
...  

HIV infection leads to reduced numbers and increased turnover of CD4+ T cells in blood. However, blood represents only 2% of the total lymphocyte pool, and information about other organs is lacking, leading to controversy about the effects of HIV infection on T-cell homeostasis. Therefore, we have determined phenotype and turnover of lymphocyte subsets in various tissues of macaques. Infection with simian immunodeficiency virus (SIV) resulted in increased proliferation rates of T cells in all organs. Despite reduced CD4 counts in blood, absolute numbers of CD4+ T cells were increased in spleen and lymph nodes and remained stable in nonlymphoid organs such as liver, lung, bone marrow, and brain during the asymptomatic phase, indicative for an altered tissue distribution. In animals killed with first signs of AIDS, total body CD4 counts and proliferation rates had returned to control levels, whereas thymocytes were almost completely absent. Our data show that a drastically increased turnover in the early stages of HIV infection, driven by a generalized immune activation rather than a homeostatic response to CD4+ T-cell destruction, is followed by exhaustion of the regenerative capacity of the immune system.


2010 ◽  
Vol 84 (8) ◽  
pp. 3845-3856 ◽  
Author(s):  
Mauro Pistello ◽  
Francesca Bonci ◽  
Elisa Zabogli ◽  
Francesca Conti ◽  
Giulia Freer ◽  
...  

ABSTRACT The envelope (Env) glycoproteins of HIV and other lentiviruses possess neutralization and other protective epitopes, yet all attempts to induce protective immunity using Env as the only immunogen have either failed or afforded minimal levels of protection. In a novel prime-boost approach, specific-pathogen-free cats were primed with a plasmid expressing Env of feline immunodeficiency virus (FIV) and feline granulocyte-macrophage colony-stimulating factor and then boosted with their own T lymphocytes transduced ex vivo to produce the same Env and interleukin 15 (3 × 106 to 10 × 106 viable cells/cat). After the boost, the vaccinees developed elevated immune responses, including virus-neutralizing antibodies (NA). Challenge with an ex vivo preparation of FIV readily infected all eight control cats (four mock vaccinated and four naïve) and produced a marked decline in the proportion of peripheral CD4 T cells. In contrast, five of seven vaccinees showed little or no traces of infection, and the remaining two had reduced viral loads and underwent no changes in proportions of CD4 T cells. Interestingly, the viral loads of the vaccinees were inversely correlated to the titers of NA. The findings support the concept that Env is a valuable immunogen but needs to be administered in a way that permits the expression of its full protective potential.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 753
Author(s):  
Mohammad Haque ◽  
Fengyang Lei ◽  
Xiaofang Xiong ◽  
Yijie Ren ◽  
Hao-Yun Peng ◽  
...  

The viral antigen (Ag)-specific CD8+ cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress the human immunodeficiency virus (HIV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the local tissues to suppress HIV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs elicit the antiviral response remain to be fully elucidated. In this study, we generated the functional HIV-1 Gag epitope SL9-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the suppression of SL9-specific iPSC-CTLs on viral replication and the protection of CD4+ T cells. A chimeric HIV-1, i.e., EcoHIV, was used to produce HIV replication in mice. We show that adoptive transfer of SL9-specific iPSC-CTLs greatly suppressed EcoHIV replication in the peritoneal macrophages and spleen in the animal model. Furthermore, we demonstrate that the adoptive transfer significantly reduced expression of PD-1 on CD4+ T cells in the spleen and generated persistent anti-HIV memory T cells. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the local tissues to suppress HIV replication and prevent CD4+ T cell exhaustion through reduction of PD-1 expression.


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