Induction of immune response in macaque monkeys infected with simian-human immunodeficiency virus having the TNF-alpha gene at an early stage of infection.
TNF-alpha has been implicated in the pathogenesis of, and the immune response against, HIV-1 infection. To clarify the roles of TNF-alpha against HIV-1-related virus infection in an SHIV-macaque model, we genetically engineered an SHIV to express the TNF-alpha gene (SHIV-TNF) and characterized the virus's properties in vivo. After the acute viremic stage, the plasma viral loads declined earlier in the SHIV-TNF-inoculated monkeys than in the parental SHIV (SHIV-NI)-inoculated monkeys. SHIV-TNF induced cell death in the lymph nodes without depletion of circulating CD4(+) T cells. SHIV-TNF provided some immunity in monkeys by increasing the production of the chemokine RANTES and by inducing an antigen-specific proliferation of lymphocytes. The monkeys immunized with SHIV-TNF were partly protected against a pathogenic SHIV (SHIV-C2/1) challenge. These findings suggest that TNF-alpha contributes to the induction of an effective immune response against HIV-1 rather than to the progression of disease at the early stage of infection.
Shimizu
Yuya
Y
Department of Veterinary Microbiology, University of Miyazaki, Miyazaki 889-2192, Japan.
Miyazaki
Yasuyuki
Y
Ibuki
Kentaro
K
Suzuki
Hajime
H
Kaneyasu
Kentaro
K
Goto
Yoshitaka
Y
Hayami
Masanori
M
Miura
Tomoyuki
T
Haga
Takeshi
T
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D018946:Chemokine CCL5 / Q000097:blood; D004274:DNA, Recombinant / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005818:Genetic Engineering; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
D000914:Antibodies, Viral; D018946:Chemokine CCL5; D004274:DNA, Recombinant; D015483:HIV Antibodies; D014409:Tumor Necrosis Factor-alpha