Goldstein H, Kollmann TR, Pettoello-Mantovani M, Katopodis NF, Gibbons C, Yurasov S; Conference on Advances in AIDS Vaccine Development.
Conf Adv AIDS Vaccine Dev 1997 Conf Adv AIDS Vaccine Dev 1997 Bethesda Md. 1997 May 4-7; 95.
Albert Einstein College of Medicine, Bronx, NY. Fax: (718) 430-8972.
Modifications we introduced into the implantation of human fetal thymus and liver under the kidney capsules of SCID mice (thy/liv-SCID-hu mice) resulted in the population of the peripheral lymphoid compartment of these mice with high numbers of human T cells. After inoculation with HIV, extensive HIV infection was detected in the lymphoid tissues of these thy/liv-SCID-hu mice, associated with high levels of plasma viremia. By measuring the decline of plasma HIV in response to ritonavir treatment, we determined that the average lifespan of extracellular HIV (0.34 days) and of productively infected cells (1.89 days) was comparable to results reported in HIV-infected humans. These mice were used to study the effectiveness of acute treatment to prevent HIV infection. Thy/liv-SCID-hu mice treated immediately after HIV inoculation with AZT/3TC/ritonavir displayed no evidence of HIV infection by co-culture even 1 month after the mice were taken off therapy. HIV infection could also be averted by acute treatment with IL-10 which prevented HIV infection in 5 of 10 mice that were examined 4 months after inoculation with HIV. The utility of this model was expanded to study mucosal transmission of HIV by subcutaneously implanting thy/liv-SCID-hu mice with human intestinal tissue approximated to maintain a lumen. Six months after implantation, the implant displayed normal histological appearance and was populated with human T cells. After introduction of HIV into the lumen of the intestinal implant, scattered HIV-infected cells were detected in the lamina propria and subsequent disseminated HIV infection occurred. These mice should be useful in studying the pathophysiology of HIV transmission and the efficacy of acute pharmacological and immunological interventions in preventing HIV infection.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Animals
- Antiretroviral Therapy, Highly Active
- Drug Therapy, Combination
- HIV Infections
- HIV Seropositivity
- Humans
- Interleukin-10
- Lamivudine
- Lymphoid Tissue
- Mice
- Mice, SCID
- Ritonavir
- T-Lymphocytes
- Thymus Gland
- Viremia
- Zidovudine
- drug therapy
- therapy
Other ID:
UI: 102225639
From Meeting Abstracts