Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1.
A small animal model that could be infected with human immunodeficiency virus 1 (HIV-1) after peripheral inoculation would greatly facilitate the study of the pathophysiology of acute HIV-1 infection. The utility of SCID mice implanted with human fetal thymus and liver (SCID-hu mice) for studying peripheral HIV-1 infection in vivo has been hampered by the requirement for direct intraimplant injection of HIV-1 and the continued restriction of the resultant HIV-1 infection to the human thymus and liver (hu-thy/liv) implant. This may have been due to the very low numbers of human T cells present in the SCID-hu mouse peripheral lymphoid compartment. Since the degree of the peripheral reconstitution of SCID-hu mice with human T cells may be a function of the hu-thy/liv implant size, we increased the quantity of hu-thy/liv tissue implanted under the renal capsule and implanted hu-thy/liv tissue under the capsules of both kidneys. This resulted in SCID-hu mice in which significant numbers of human T cells were detected in the peripheral blood, spleens, and lymph nodes. After intraimplant injection of HIV-1 into these modified SCID-hu mice, significant HIV-1 infection was detected by quantitative coculture not only in the hu-thy/liv implant, but also in the spleen and peripheral blood. This indicated that HIV-1 infection can spread from the thymus to the peripheral lymphoid compartment. More importantly, a similar degree of infection of the hu-thy/liv implant and peripheral lymphoid compartment occurred after peripheral intraperitoneal inoculation with HIV-1. Active viral replication was indicated by the detection of HIV-1 gag DNA, HIV-1 gag RNA, and spliced tat/rev RNA in the hu-thy/liv implants, peripheral blood mononuclear cells (PBMC), spleens, and lymph nodes of these HIV-1-infected SCID-hu mice. As a first step in using our modified SCID-hu mouse model to investigate the pathophysiological consequences of HIV-1 infection, the effect of HIV-1 infection on the expression of human cytokines shown to enhance HIV-1 replication was examined. Significantly more of the HIV-1-infected SCID-hu mice expressed mRNA for human tumor necrosis factors alpha and beta, and interleukin 2 in their spleens, lymph nodes, and PBMC than did uninfected SCID-hu mice. This suggested that HIV-1 infection in vivo can stimulate the expression of cytokine mRNA by human T cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Kollmann
T R
TR
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461.
Pettoello-Mantovani
M
M
Zhuang
X
X
Kim
A
A
Hachamovitch
M
M
Smarnworawong
P
P
Rubinstein
A
A
Goldstein
H
H
D000818:Animals; D001483:Base Sequence; D017690:Cell Transplantation; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004247:DNA; D004195:Disease Models, Animal; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008099:Liver / Q000166:cytology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology
D016207:Cytokines; D004247:DNA