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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Human immunodeficiency virus type 1 derivative with 7% simian immunodeficiency virus genetic content is able to
Tatsuhiko Igarashi1, Ranjini Iyengar, Russel A Byrum
1Laboratory of Molecular Microbiology, NIAID, NIH, Bldg. 4, Room 315, 4 Center Drive, MSC 0460, Bethesda, MD 20892-0460, USA.
Abstract:
A human immunodeficiency virus type 1 (HIV-1) derivative (HIV(NL-DT5R)) containing sequences encoding a 7-amino-acid segment of CA and the entire vif gene from simian immunodeficiency virus (SIV) was previously shown to establish spreading infections in cultured macaque peripheral blood mononuclear cells. To assess its replicative and disease-inducing properties in vivo, HIV(NL-DT5R) was inoculated into pig-tailed macaques. HIV(NL-DT5R) generated plasma viremia in all five of the monkeys and elicited humoral responses against all of the HIV-1 structural proteins but did not cause CD4(+) T-lymphocyte depletion or clinical disease. Additional adaptation will be required to optimize infectivity in vivo.
Insights
This study investigated a novel human immunodeficiency virus type 1 (HIV-1) derivative in macaques. The virus showed replication but did not induce disease, indicating a need for further adaptation for in vivo infectivity.
Area of Science:
- Virology
- Immunology
- Primate models
Background:
- A novel human immunodeficiency virus type 1 (HIV-1) derivative, HIV(NL-DT5R), was created using simian immunodeficiency virus (SIV) genetic material.
- This derivative was previously shown to infect macaque peripheral blood mononuclear cells in vitro.
Purpose of the Study:
- To evaluate the in vivo replicative capacity and disease-inducing potential of the HIV(NL-DT5R) derivative.
- To determine if the chimeric virus could establish a persistent infection and cause pathogenesis in a relevant animal model.
Main Methods:
- Pig-tailed macaques were inoculated with the HIV(NL-DT5R) derivative.
- Plasma viremia, humoral immune responses, and CD4(+) T-lymphocyte counts were monitored.
- Clinical signs of disease were assessed.
Main Results:
- All inoculated macaques developed plasma viremia after HIV(NL-DT5R) infection.
- Humoral immune responses against HIV-1 structural proteins were detected in all animals.
- No significant CD4(+) T-lymphocyte depletion or clinical disease was observed.
Conclusions:
- The HIV(NL-DT5R) derivative can replicate and elicit an immune response in vivo in pig-tailed macaques.
- The current construct does not induce significant pathogenesis or CD4(+) T-lymphocyte depletion.
- Further adaptation of the virus is necessary to enhance its in vivo infectivity and disease-inducing potential.
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