Pereboeva L, Komarova S, Rakasz E, Bucy P; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 71 (abstract no. 94).
Univ of Alabama at Birmingham.
Background: A key to understanding HIV pathogenesis is characterization of dynamics of viral replication in lymphoid tissue. Since the different lymphoid tissues have multiple distinct characteristics, but all may contribute to in vivo infection, we have performed quantitative analyses of both cellular and viral components in multiple tissue sites of rhesus macaques infected with a simian-human immunodeficiency virus (SHIV). Methods: Adult rhesus macaques infected by intra- rectal instillation with SHIV89.6PD were sacrificed 10 days, 10 weeks, or more than 6 months after infection. Lymphocytes were directly counted in blood, multiple lymph nodes, spleen, thymus, and bone marrow and analyzed by flow cytometry. Frozen blocks were prepared from these lymphoid tissues and different regions of the gastrointestinal tract. These tissues were analyzed for frequency of viral RNA (vRNA)-expressing cells by in situ hybridization and for activation status of lymphoid subsets by mAb staining. The amounts of vRNA and vDNA in different tissues and plasma were determined using a sensitive real-time RT-PCR assay. Results: The real-time PCR assay was shown to be accurate and sensitive to about 50 copies/10(6) cells from tissue and 50 copies/ml in plasma. Two animals had initial high level viremia but had <50 copies/ml plasma vRNA at the time of necropsy at 10 weeks. These animals still had vRNA+ cells in lymphoid tissues, albeit at very low frequencies of between 0.1 and 0.3 cells/10(6). One animal had several clusters of vRNA+ cells in the white pulp of the spleen despite undetectable plasma virus. Two animals had higher viral loads and correspondingly higher frequencies of vRNA+ cells in multiple tissues. The localization of these cells was primarily in the periarteriolar lymphoid sheath of the spleen, in submucosal lymphoid aggregates of the colon, and in the follicular cortex of lymph nodes. Conclusions: The correspondence of the frequency of vRNA+ cells in lymphoid tissues and quantitative amount of plasma vRNA is similar to that previously found in humans between lymph node biopsies and plasma. Detection of distinct vRNA+ cells in animals with undetectable plasma virus indicates that viral replication persists, presumably controlled by host mechanisms.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Adult
- Animals
- Anti-HIV Agents
- HIV
- HIV Infections
- Humans
- Lymph Nodes
- Lymphocytes
- Lymphoid Tissue
- Macaca mulatta
- RNA, Viral
- Simian Acquired Immunodeficiency Syndrome
- Spleen
- Thymus Gland
- Viral Load
- Viremia
Other ID:
UI: 102243874
From Meeting Abstracts