Assessment of oral transmission using cell-free human immunodeficiency virus-1 in mice reconstituted with human peripheral blood leucocyte

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)

Download Full-text

Alcohol Intake Increases Human Immunodeficiency Virus Type 1 Replication in Human Peripheral Blood Mononuclear Cells

The Journal of Infectious Diseases ◽

10.1093/infdis/167.4.789 ◽

1993 ◽

Vol 167 (4) ◽

pp. 789-797 ◽

Cited By ~ 70

Author(s):

O. Bagasra ◽

A. K. Balla ◽

H. W. Lischner ◽

R. J. Pomerantz

Keyword(s):

Human Immunodeficiency Virus ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Alcohol Intake ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Immunodeficiency Virus ◽

Blood Mononuclear Cells

Download Full-text

Identification and culture of Kaposi's sarcoma-like spindle cells from the peripheral blood of human immunodeficiency virus-1-infected individuals and normal controls [see comments]

Blood ◽

10.1182/blood.v84.8.2711.bloodjournal8482711 ◽

1994 ◽

Vol 84 (8) ◽

pp. 2711-2720 ◽

Cited By ~ 4

Author(s):

PJ Browning ◽

JM Sechler ◽

M Kaplan ◽

RH Washington ◽

R Gendelman ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

High Risk ◽

Peripheral Blood ◽

Vascular Endothelial Cells ◽

Peripheral Blood Mononuclear ◽

Spindle Cells ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Human Immunodeficiency Virus 1

We examined 26 patients with human immunodeficiency virus-1 (HIV-1)- associated Kaposi′s sarcoma (KS), and 76 HIV-1-infected (HIV-1+) people without KS or uninfected (HIV-1-) controls for the presence of circulating KS-like spindle cells. Adherent cells that had spindle morphology and several characteristics of spindle cells of KS lesions (KS cells) were identified in the peripheral blood mononuclear cell fraction only after culture in the presence of conditioned medium (CM) from activated lymphocytes. The peripheral blood-derived spindle cells (PBsc) expressed a variety of endothelial cell markers, such as Ulex europaeus I lectin, EN4, EN2/3, EN7/44, CD13, CD34, CD36, CD54, ELAM-1, and HLA-DR. However, they were negative for CD2, CD19, PaIE, and factor VIII-related antigen. The PBsc produced angiogenic factors as evidenced by the ability of CM from these cells to promote growth of normal vascular endothelial cells. In addition, subcutaneously injected PBsc stimulated angiogenesis in vivo in athymic nude mice. We determined that the number of PBsc grown from the peripheral blood of HIV-1+ patients with KS or at high risk to develop KS were increased by 78- fold (P = .0001) and 18-fold (P = .005), respectively, when compared with HIV-1- controls. The number of spindle cells cultured from the HIV- 1+ patients at low risk for developing KS, eg, HIV-1+ injection drug users, showed no statistical increase when compared with HIV-1- controls. The presence of increased PBsc with characteristics of KS cells in HIV-1+ KS patients or patients at high risk for developing KS gives insights into the origin of KS cells and may explain the multifocal nature of the disease. In addition, this may be useful in predicting the risk of KS development.

Download Full-text