High viral burden in lymph nodes during early stages of HIV-1 infection

Lafeuillade, Alain; Tamalet, Catherine; Pellegrino, Pierre; Tourres, Christian; Yahi, Nouara; Vignoli, C.; Quilichini, R; P, de Micco

doi:10.1097/00002030-199311000-00019

Cited by 15 publications

(8 citation statements)

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“…A gradient still exists, however: the proportion of CD4 ϩ T cells carrying replication competent HIV-1 is approximately 40 times higher in tonsillar tissue than in peripheral blood. These results on viral load are comparable to results obtained by ID 50 methodology (17) and quantitative PCR (18) using cells from lymph nodes. Also, early studies suggested a very low prevalence of actively HIV-1-producing cells in lymph nodes (19,20).…”

Section: Discussionsupporting

confidence: 87%

Correlates of latent and productive HIV type-1 infection in tonsillar CD4 ⁺ T cells

Røsok

Brinchmann

Voltersvik

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Correlates of virus load and characteristics of virus-producing cells in tonsillar tissue were investigated. Our results suggest that when less than 1:100 tonsillar CD4 ؉ T cells from individuals infected with HIV type-1 (HIV-1) contain replication competent provirus, the level of CD4 ؉ T cells in tonsils is comparable to that observed in uninfected individuals. Virus load at or above this level was associated with low CD4 cell numbers in tonsillar tissue. Only a few percent of all infected T cells in tonsillar tissue were active virus producers, with minor differences observed between individuals. Plasma viremia was found to correlate with infectious virus load in tonsillar tissue. With less than 1:1,000 of CD4 cells in lymphoid tissues being involved in active virus production, direct cytopathic effect by HIV-1 on infected CD4 cells is unlikely to fully explain the immunodeficiency seen in AIDS.HIV type-1 (HIV-1) predominantly infects T cells that express CD4 (1). However, through years of clinically latent HIV-1 infection the proportion of CD4 ϩ T cells in blood carrying replication competent provirus is typically less than 1:1,000 (1, 2). More recent studies have suggested higher viral loads in lymphoid tissues (3). Still, the proportion of HIV-1-producing cells has been considered by many to be insufficient to fully explain the overall loss of CD4 ϩ T cells suggested by the low levels of CD4 ϩ T cells in blood (4). New data estimating a production of up to 10 10 HIV-1 particles and a continuously high turnover of CD4 ϩ T cells has profoundly affected current thinking on the immunopathogenesis of AIDS (5-8). These estimations were made by measurement of the concentration of CD4 cells in peripheral blood and virions in plasma after in vivo treatment with potent inhibitors of HIV-1 replication (5-7). However, only approximately 2% of all lymphocytes are found in peripheral blood; the majority of lymphocytes are located in lymphoid tissues. Thus, studies of cellular changes and virus load in lymphoid tissues are required to fully understand the forces driving the development of AIDS. The palatine tonsils, containing lymphoid tissue with characteristics similar to both lymph node tissue and gut-associated lymphoid tissue, may yield biopsy material suitable for such studies. Examining biopsies of tonsillar tissue from HIV-1-infected individuals at different clinical stages of infection, we have recently shown that in tonsillar tissue from asymptomatic HIV-1-positive individuals, CD4 ϩ T cells are maintained at levels similar to those observed in uninfected controls, despite reduced CD4 ϩ T cell counts in blood (9).The present study focuses on correlates of virus load in tonsillar tissue. We show evidence suggesting that as long as the proportion of provirus-containing CD4 cells is below 1:100, the level of CD4 cells in lymphoid tissues remains relatively unaffected. Virus load at or above this threshold of infection was associated with low levels of tonsillar tissue CD4 ϩ T cells. Moreover, we show that o...

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Section: Discussionsupporting

confidence: 87%

Correlates of latent and productive HIV type-1 infection in tonsillar CD4 ⁺ T cells

Røsok

Brinchmann

Voltersvik

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…9 HIV-1 RNA production is believed to be an "all or none" phenomenon resulting in high bursts of HIV-1 from a small proportion of the CD4 1 T cells actively producing virus. 1,[4][5][6]35 Further, this group found less trapping of FDC-associated viruses as compared with previous reports and explained the discrepancy as caused by differences in sensitivity between the histochemical techniques used. [1][2][3]6,7,9,18,43 We took advantage of this information to calculate the total number of HIV-1 RNA-producing CD4 1 cells.…”

Section: Discussioncontrasting

confidence: 41%

“…1,4,5 However, in lymphoid tissue, the frequency of CD4 1 T cells with replication-competent proviral DNA is less than 1% during the asymptomatic period 1,4,5 and less than 1 in 1000 CD4 1 T cells are actually involved in active virus replication. 5,6 The current assumption is that HIV-1 virions trapped in the follicular dendritic cell (FDC) network account for the major part of HIV-1 RNA found in lymphoid tissue in chronic HIV-1 infection.…”

Section: Introductionmentioning

confidence: 99%

Residual Human Immunodeficiency Virus Type 1 Infection in Lymphoid Tissue during Highly Active Antiretroviral Therapy: Quantitation and Virus Characterization

Dyrhol‐Riise

Voltersvik²,

Berg³

et al. 2001

AIDS Research and Human Retroviruses

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HIV-1 can persist in infected patients despite undetectable plasma viremia. To characterize the residual viral load, repetitive blood and tonsillar samples were collected from 11 HIV-1-positive individuals before and during 96 weeks of therapy with zidovudine, lamivudine, and indinavir. HIV-1 RNA in tonsils was quantified by RT-PCR and infectious HIV-1 provirus by the limiting dilution assay. Genotypic resistance analyses and biological characterization were performed on plasma virus, blood, and tonsillar isolates. Tonsillar infectious HIV-1 provirus and HIV-1 RNA declined by 2 and 3 log(10), respectively, but 10(3)-10(4) cells, less than 0.5% of the total body CD4(+) T cell population carrying infectious HIV-1 provirus, remained involved in active viral replication of drug-sensitive R5 viruses. Thus, the dominant HIV-1 residual infection consists of < or = 10(6) latently infected CD4(+) cells. Plasma HIV-1 RNA decline of > 1.5 log(10) during the first 2 weeks of therapy may indicate low levels of this latent reservoir. Whereas the reservoir of latently infected cells remains stable, actively replicating HIV-1 continuously declines during prolonged antiretroviral therapy. Thus, although viral eradication seems unlikely, antiretroviral therapy may induce an extended period of virologic latency in HIV-1-positive individuals.

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“…Various studies have shown that infected CD4 þ T lymphocytes are sequestered in the lymph nodes during HIV-1 infection [1,2] and that viral replication is active in these tissues. HIV-1 viral load is higher in lymph nodes than in peripheral blood during the asymptomatic phase of HIV-1 infection and this dichotomy is reduced during progression to the late stages of HIV disease [2][3][4][5][6]. Limited studies on HIV-2 proviral load in peripheral blood of asymptomatic subjects have shown that it is lower than HIV-1 and is inversely correlated with the percentage of CD4 þ cells [7][8][9], but there is no information on lymph node tropism of HIV-2.…”

Section: Introductionmentioning

confidence: 99%

Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection

Jobe

Ariyoshi

Marchant

et al. 1999

Clinical and Experimental Immunology

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SUMMARYProviral load as well as lymphocyte phenotype and function were compared in peripheral blood and lymph node compartments of 17 HIV-1, 12 HIV-2 and three dually infected patients with lymphadenopathy. The mean percentage (95% confidence interval (CI)) of CD4 þ cells was higher in lymph node mononuclear cells (LNMC) than in peripheral blood mononuclear cells (PBMC) in both infections, being 26·7% (21·1%, 32·3%) and 15·3% (10·4%, 20·2%), respectively, for HIV-1-infected patients (P ¼ 0·0001) and 32·3% (22·7%, 41·9%) and 22·1% (13·6%, 30·6%), respectively, for HIV-2-infected patients (P ¼ 0·02). In both types of infection, proviral load adjusted for number of CD4 þ cells was higher in LNMC than in PBMC: the geometric mean (95% CI) was 8937 (4991; 16 003) and 4384 (2260; 8503), respectively, for HIV-1 patients (P ¼ 0·02) and 1624 (382; 6898) and 551 (147; 2058) DNA copies, respectively, for HIV-2 patients (P ¼ 0·05). Proviral load in both compartments was closely correlated (HIV-1, r ¼ 0·60, P ¼ 0·01; and HIV-2, r ¼ 0·83, P ¼ 0·0003). In both infections, proliferation and interferon-gamma (IFN-g) production in response to purified protein derivative (PPD) was lower in LNMC than in PBMC, both of which, in turn, were lower than in healthy controls. These results indicate that in HIV-2 as in HIV-1 infection, infected cells have a tropism for the lymph nodes resulting in higher viral load in this compartment and lower lymphocyte responses to the recall antigen PPD which may increase susceptibility to tuberculosis.

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High viral burden in lymph nodes during early stages of HIV-1 infection

Cited by 15 publications

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Correlates of latent and productive HIV type-1 infection in tonsillar CD4 ⁺ T cells

Correlates of latent and productive HIV type-1 infection in tonsillar CD4 ⁺ T cells

Residual Human Immunodeficiency Virus Type 1 Infection in Lymphoid Tissue during Highly Active Antiretroviral Therapy: Quantitation and Virus Characterization

Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection

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High viral burden in lymph nodes during early stages of HIV-1 infection

Cited by 15 publications

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Correlates of latent and productive HIV type-1 infection in tonsillar CD4 + T cells

Correlates of latent and productive HIV type-1 infection in tonsillar CD4 + T cells

Residual Human Immunodeficiency Virus Type 1 Infection in Lymphoid Tissue during Highly Active Antiretroviral Therapy: Quantitation and Virus Characterization

Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection

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Correlates of latent and productive HIV type-1 infection in tonsillar CD4 ⁺ T cells

Correlates of latent and productive HIV type-1 infection in tonsillar CD4 ⁺ T cells