Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jun 11;9(2):e98636.
doi: 10.1371/journal.pone.0098636. eCollection 2014.

Lipopolysaccharide induces immune activation and SIV replication in rhesus macaques of Chinese origin

Rong Bao  1 , Ke Zhuang  1 , Jinbiao Liu  1 , Jianguo Wu  2 , Jieliang Li  3 , Xu Wang  3 , Wen-Zhe Ho  4
Affiliations

Lipopolysaccharide induces immune activation and SIV replication in rhesus macaques of Chinese origin

Rong Bao et al. PLoS One. .

Abstract

Background: Chronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS) in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We thus investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV)-infected rhesus macaques of Chinese origin.

Methods: The animals were inoculated intravenously with SIVmac239. The levels of plasma viral load and host inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio and systemic immune activation markers were examined by flow cytometric analysis of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels were determined using biochemistry analyzer. The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL) test.

Results: The animals inoculated with SIVmac239 became infected as evidenced by the increased plasma levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected animals induced a transient increase of plasma SIV RNA and immune activation, which was indicated by the elevated expression of the inflammatory cytokines and CD4+HLA-DR+ T cells in PBMCs.

Conclusions: These data support the concept that LPS is a driving factor in systemic immune activation of HIV disease.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: WZH is a PLOS ONE Editorial Board member. This does not alter the authors’ adherence to PLOS ONE Editorial policies and criteria.

Figures

Figure 1
Figure 1. SIV infection of Chinese rhesus monkeys.
Six animals were intravenously inoculated with SIVmac239 (103 TCID50). Blood samples were collected from the animals at the indicated time points postinfection. A: Plasma levels of SIV GAG gene RNA were measured by real-time PCR. B: CD4/CD8 ratios were measured by flow cytometry. C: Average SIV loads and CD4/CD8 ratios (mean ± SEM) of SIV-infected animals.
Figure 2
Figure 2. Effect of LPS on SIV replication.
SIV-infected animals were intravenously injected with either a single dose of LPS (50 µg/kg; solid circles and lines, n = 3) or saline (open circle and dashed lines, n = 3) at 45 weeks postinfection. The plasma samples were collected at the indicated time points after LPS treatment. A: The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL) test. B: SIV loads were measured by real-time PCR for SIV GAG gene expression.
Figure 3
Figure 3. Effect of LPS on WBC, neutrophils and CRP.
SIVmac239-infected animals were intravenously injected with either LPS (50 µg/kg; solid circles and lines, n = 3) or saline (open circle and dashed lines, n = 3) at 45 weeks postinfection. At the indicated time points after LPS administration, white blood cell (WBC) counts (A), neutrophil counts (B), and C Reactive Protein (CRP) levels (C) were determined by a biochemistry analyzer.
Figure 4
Figure 4. Effect of LPS on CD4/CD8 ratio, counts of CD4+ T cells and frequency of CD4+HLA-DR+ T cells.
SIVmac239-infected animals were intravenously injected with either LPS (50 µg/kg; solid circles and lines, n = 3) or saline (open circle and dashed lines, n = 3) at 45 weeks postinfection. At the indicated time points after LPS administration, the CD4/CD8 ratios (A), total CD4+ T cell counts (B), and CD4+HLA-DR+ T cell percentage in PBMCs (C) were determined by flow cytometry.
Figure 5
Figure 5. Effect of LPS on inflammatory cytokines in PBMCs.
SIVmac239-infected animals were intravenously injected with a single dose of LPS (50 µg/kg, solid circles and lines, n = 3) or saline (open circle and dashed lines, n = 3) at 45 weeks postinfection. Blood samples were collected at indicated time points post-LPS administration and PBMCs were isolated. The levels of cytokines (IL-6, IL-8, IFN-α, and TNF-α) in PBMCs were determined by real-time PCR and normalized to GAPDH mRNA. Data are expressed as fold of control (before LPS administration, cytokine mRNA/GAPDH mRNA, which was defined as 1).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, et al. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 12: 1365–1371. - PubMed
    1. Jiang W, Lederman MM, Hunt P, Sieg SF, Haley K, et al. (2009) Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J Infect Dis 199: 1177–1185. - PMC - PubMed
    1. Zhou Y, Bao R, Haigwood NL, Persidsky Y, Ho W-z (2013) SIV infection of rhesus macaques of Chinese origin: a suitable model for HIV infection in humans. Retrovirology 10: 89. - PMC - PubMed
    1. Desrosiers R (1995) Non-human primate models for AIDS vaccines. AIDS (London, England) 9: S137. - PubMed
    1. Joag SV (2000) Primate models of AIDS. Microbes and infection 2: 223–229. - PubMed

Publication types