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Retrovirology. 2017 Mar 9;14(1):17. doi: 10.1186/s12977-017-0344-7.

A mature macrophage is a principal HIV-1 cellular reservoir in humanized mice after treatment with long acting antiretroviral therapy.

Author information

1
Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.
2
Department of Pharmacology and Experimental Neuroscience, 985880 Nebraska Medical Center, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA. hegendel@unmc.edu.

Abstract

BACKGROUND:

Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1ADA-infected NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency. At 6 weeks of infection animals were divided into four groups. One received long-acting (LA) cabotegravir (CAB) and rilpivirine (RVP) (2ART), a second received LA CAB, lamivudine, abacavir and RVP (4ART), a third were left untreated and a fourth served as an uninfected control. After 4 weeks of LA ART treatment, blood, spleen and bone marrow (BM) cells were collected then phenotypically characterized. CD4+ T cell subsets, macrophages and hematopoietic progenitor cells were analyzed for HIV-1 nucleic acids by droplet digital PCR.

RESULTS:

Plasma viral loads were reduced by two log10 or to undetectable levels in the 2 and 4ART regimens, respectively. Numbers and distributions of CD4+ memory and regulatory T cells, macrophages and hematopoietic progenitor cells were significantly altered by HIV-1 infection and by both ART regimens. ART reduced viral DNA and RNA in all cell and tissue compartments. While memory cells were the dominant T cell reservoir, integrated HIV-1 DNA was also detected in the BM and spleen macrophages in both regimen-treated mice.

CONCLUSION:

Despite vigorous ART regimens, HIV-1 DNA and RNA were easily detected in mature macrophages supporting their potential role as an infectious viral reservoir.

KEYWORDS:

Antiretroviral therapy; HIV-1; Humanized mice; Monocyte–macrophage; T effector cells; Viral reservoirs

PMID:
28279181
PMCID:
PMC5345240
DOI:
10.1186/s12977-017-0344-7
[Indexed for MEDLINE]
Free PMC Article

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