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Myeloid and CD4 T Cells Comprise the Latent Reservoir in Antiretroviral Therapy-Suppressed SIVmac251-Infected Macaques
- Source :
- mBio, mBio, Vol 10, Iss 4, p e01659-19 (2019), mBio, Vol 10, Iss 4 (2019)
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- This study provides further evidence that the latent reservoir is comprised of both CD4+ T cells and myeloid cells. The data presented here suggest that CD4+ T cells and macrophages found throughout tissues in the body can contain replication-competent SIV and contribute to rebound of the virus after treatment interruption. Additionally, we have shown that monocytes in blood contain latent virus and, though not considered a reservoir themselves due to their short life span, could contribute to the size of the latent reservoir upon entering the tissue and differentiating into long-lived macrophages. These new insights into the size and location of the SIV reservoir using a model that is heavily studied in the HIV field could have great implications for HIV-infected individuals and should be taken into consideration with the development of future HIV cure strategies.<br />Human immunodeficiency virus (HIV) eradication or long-term suppression in the absence of antiretroviral therapy (ART) requires an understanding of all viral reservoirs that could contribute to viral rebound after ART interruption. CD4 T cells (CD4s) are recognized as the predominant reservoir in HIV type 1 (HIV-1)-infected individuals. However, macrophages are also infected by HIV-1 and simian immunodeficiency virus (SIV) during acute infection and may persist throughout ART, contributing to the size of the latent reservoir. We sought to determine whether tissue macrophages contribute to the SIVmac251 reservoir in suppressed macaques. Using cell-specific quantitative viral outgrowth assays (CD4-QVOA and MΦ-QVOA), we measured functional latent reservoirs in CD4s and macrophages in ART-suppressed SIVmac251-infected macaques. Spleen, lung, and brain in all suppressed animals contained latently infected macrophages, undetectable or low-level SIV RNA, and detectable SIV DNA. Silent viral genomes with potential for reactivation and viral spread were also identified in blood monocytes, although these cells might not be considered reservoirs due to their short life span. Additionally, virus produced in the MΦ-QVOA was capable of infecting healthy activated CD4s. Our results strongly suggest that functional latent reservoirs in CD4s and macrophages can contribute to viral rebound and reestablishment of productive infection after ART interruption. These findings should be considered in the design and implementation of future HIV cure strategies.
- Subjects :
- CD4-Positive T-Lymphocytes
Male
Myeloid
viruses
Simian Acquired Immunodeficiency Syndrome
Spleen
HIV Infections
Genome, Viral
Biology
medicine.disease_cause
Virus Replication
Microbiology
Virus
Monocytes
Clinical Science and Epidemiology
03 medical and health sciences
0302 clinical medicine
Latent Virus
Virology
medicine
Animals
Myeloid Cells
Lung
latency
030304 developmental biology
0303 health sciences
Macrophages
RNA
HIV
Simian immunodeficiency virus
Viral Load
Antiretroviral therapy
Macaca mulatta
QR1-502
3. Good health
Virus Latency
Disease Models, Animal
medicine.anatomical_structure
SIV
Anti-Retroviral Agents
Simian Immunodeficiency Virus
030217 neurology & neurosurgery
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 21507511
- Volume :
- 10
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- mBio
- Accession number :
- edsair.doi.dedup.....60d02a179c830db7b65209f40c4336ce