Highly active antiretroviral therapy potently suppresses HIV infection in humanized Rag2-/-gammac-/- mice.
Humanized Rag2(-/-)gamma(c)(-/-) mice (Hu-DKO mice) become populated with functional human T cells, B cells, and dendritic cells following transplantation with human hematopoietic stem cells (HSC) and represent an improved model for studying HIV infection in vivo. In the current study we demonstrated that intrasplenic inoculation of hu-DKO mice with HIV-1 initiated a higher level of HIV infection than intravenous or intraperitoneal inoculation, associated with a reciprocal decrease in peripheral CD4(+) T cells and increase in peripheral CD8(+) T cells. HIV infection by intrasplenic injection increased serum levels of human IgG and IgM including human IgM and IgG specific for HIV-1 gp120. There was a significant inverse correlation between the level of HIV-1 infection and the extent of CD4(+) T cell depletion. Highly active antiretroviral therapy (HAART) initiated 1 week after HIV-1 inoculation markedly suppressed HIV-1 infection and prevented CD4(+) T cell depletion. Taken together, these findings demonstrate that intrasplenic injection of hu-DKO mice with HIV is a more efficient route of HIV infection than intravenous or intraperitoneal injection and generates increased infection associated with an increased anti-HIV humoral response. This animal model can serve as a valuable in vivo model to study the efficacy of anti-HIV therapies.
Sango
Kaori
K
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Joseph
Aviva
A
Patel
Mahesh
M
Osiecki
Kristin
K
Dutta
Monica
M
Goldstein
Harris
H
D000818:Animals; D000831:Animals, Newborn; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004195:Disease Models, Animal; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000172:deficiency*
D019380:Anti-HIV Agents; D004268:DNA-Binding Proteins; D015483:HIV Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C499308:Rag2 protein, mouse; D015375:Receptors, Interleukin-2