Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1

Tobias R. Kollmann, Massimo Pettoello-Mantovani, Xiajun Zhuang, Ana Kim, Moshe Hachamovitch, Pam Smarnworawong, Arye Rubinstein, Harris Goldstein

Research output: Contribution to journalArticle

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Abstract

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 α and β, 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. Our modified SCID-hu mice may provide an improved model for studying the pathophysiology of HIV-1 infection in vivo and for investigating the effects of anti-HIV interventions on the prevention of disseminated HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)513-522
Number of pages10
JournalJournal of Experimental Medicine
Volume179
Issue number2
StatePublished - Feb 1 1994

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SCID Mice
Virus Diseases
HIV-1
Thymus Gland
Liver
Spleen
T-Lymphocytes
Lymph Nodes
Capsules
Blood Cells
RNA
Cytokines
Kidney
Messenger RNA
Injections

ASJC Scopus subject areas

  • Immunology

Cite this

Kollmann, T. R., Pettoello-Mantovani, M., Zhuang, X., Kim, A., Hachamovitch, M., Smarnworawong, P., ... Goldstein, H. (1994). Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1. Journal of Experimental Medicine, 179(2), 513-522.

Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1. / Kollmann, Tobias R.; Pettoello-Mantovani, Massimo; Zhuang, Xiajun; Kim, Ana; Hachamovitch, Moshe; Smarnworawong, Pam; Rubinstein, Arye; Goldstein, Harris.

In: Journal of Experimental Medicine, Vol. 179, No. 2, 01.02.1994, p. 513-522.

Research output: Contribution to journalArticle

Kollmann, TR, Pettoello-Mantovani, M, Zhuang, X, Kim, A, Hachamovitch, M, Smarnworawong, P, Rubinstein, A & Goldstein, H 1994, 'Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1', Journal of Experimental Medicine, vol. 179, no. 2, pp. 513-522.
Kollmann TR, Pettoello-Mantovani M, Zhuang X, Kim A, Hachamovitch M, Smarnworawong P et al. Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1. Journal of Experimental Medicine. 1994 Feb 1;179(2):513-522.
Kollmann, Tobias R. ; Pettoello-Mantovani, Massimo ; Zhuang, Xiajun ; Kim, Ana ; Hachamovitch, Moshe ; Smarnworawong, Pam ; Rubinstein, Arye ; Goldstein, Harris. / Disseminated human immunodeficiency virus 1 (HIV-1) infection in SCID-hu mice after peripheral inoculation with HIV-1. In: Journal of Experimental Medicine. 1994 ; Vol. 179, No. 2. pp. 513-522.
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