Therapy of "SHIV" infected macaques with liposomes delivering antisense interleukin-4 DNA.
OBJECTIVE
To explore the effects of antisense (AS) interleukin (IL)-4 on virus replication and CD8+ T-cell responses in lymph nodes and blood of macaques infected with simian human immunodeficiency virus, SHIV(89.6)P.


METHODS
Six macaques were inoculated with simian human immunodeficiency virus (SHIV(89.6)P). Seven days later, four of the animals were given 1 mg AS IL-4 plasmid complexed with Megafectin liposome, intravenously, and two of these received a second injection of the same material on day 9. All six macaques were killed at 2 weeks post infection (pi) and monitored for viral RNA and CD8+ T cells in blood and lymph nodes by real-time reverse transcriptase-polymerase chain reaction, flow cytometry and immunohistochemistry.


RESULTS
In contrast to the lymph nodes from virus control animals, the lymph nodes of AS IL-4-treated animals had a significant reduction in viral loads and reduced depletion of cells from the nodes. There was an increase in CD8+ T cells in the nodes, and many of the cells expressed granzyme B, suggesting functional activation. This trend of virus reduction and increased CD8+ T cell numbers was also reflected in blood.


CONCLUSIONS
The therapeutic effect of the AS IL-4 suggests indirectly that the acute immunosuppressive disease caused by SHIVs is mediated, in part, by IL-4 that causes enhanced virus replication by suppressing anti-viral CD8+ T-cell responses, and that this effect was reduced by treatment of the animals with AS IL-4.
Dhillon
Navneet K
NK
Department of Microbiology, Immunology and Molecular Genetics, Marion Merrell Dow Laboratory of Viral Pathogenesis, Emory University, Atlanta, Georgia, USA.
Dhillon
Sukhbir
S
Chebloune
Yahia
Y
Pinson
David
D
Villinger
Francois
F
Kumar
Anil
A
Narayan
Opendra
O
Buch
Shilpa
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016373:DNA, Antisense / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D008081:Liposomes; D008198:Lymph Nodes / Q000821:virology; D018655:Lymphocyte Count; D008252:Macaca fascicularis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D019562:Viral Load; D014779:Virus Replication
D016373:DNA, Antisense; D008081:Liposomes; D015847:Interleukin-4