Evidence map›Paper›PMID 31597776›Full record

ArticleJournal of virology2019

Evaluating the Intactness of Persistent Viral Genomes in Simian Immunodeficiency Virus-Infected Rhesus Macaques after Initiating Antiretroviral Therapy within One Year of Infection.

Samuel Long, Christine M Fennessey, Laura Newman, Carolyn Reid, Sean P O'Brien, Yuan Li, Gregory Q Del Prete, Jeffrey D Lifson, Robert J Gorelick, Brandon F Keele

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 31 citations in OpenAlex.

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  14. Intracellular mono-ADP-ribosyltransferases at the host-virus interphase.Cellular and molecular life sciences : CMLS · 2022
    Review
  15. Article
  16. Review
  17. HIV Reservoirs: Modeling, Quantification, and Approaches to a Cure.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  18. Review
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Samuel Long *AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Christine M Fennessey *AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Laura NewmanAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Carolyn ReidAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Sean P O'BrienAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Yuan LiAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Gregory Q Del PreteAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Jeffrey D LifsonAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Robert J GorelickAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Brandon F KeeleAIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA keelebf@mail.nih.gov.ORCID 0000-0002-2381-1151
Frederick National Laboratory for Cancer Research · US

Funding

CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

The major obstacle to more-definitive treatment for HIV infection is the early establishment of virus that persists despite long-term combination antiretroviral therapy (cART) and can cause recrudescent viremia if cART is interrupted. Previous studies of HIV DNA that persists despite cART indicated that only a small fraction of persistent viral sequences was intact. Experimental simian immunodeficiency virus (SIV) infections of nonhuman primates (NHPs) are essential models for testing interventions designed to reduce the viral reservoir. We studied the viral genomic integrity of virus that persists during cART under conditions typical of many NHP reservoir studies, specifically with cART started within 1 year postinfection and continued for at least 9 months. The fraction of persistent DNA in SIV-infected NHPs starting cART during acute or chronic infection was assessed with a multiamplicon, real-time PCR assay designed to analyze locations that are regularly spaced across the viral genome to maximize coverage (collectively referred to as "tile assay") combined with near-full-length (nFL) single-genome sequencing. The tile assay is used to rapidly screen for major deletions, with nFL sequence analysis used to identify additional potentially inactivating mutations. Peripheral blood mononuclear cells (PBMC) from animals started on cART within 1 month of infection, sampled at least 9 months after cART initiation, contained at least 80% intact genomes, whereas those from animals started on cART 1 year postinfection and treated for 1 year contained intact genomes only 47% of the time. The most common defect identified was large deletions, with the remaining defects caused by APOBEC-mediated mutations, frameshift mutations, and inactivating point mutations. Overall, this approach can be used to assess the intactness of persistent viral DNA in NHPs.

Indexed as

AnimalsAnti-Retroviral AgentsAntiretroviral Therapy, Highly ActiveCD4-Positive T-LymphocytesDNA, ViralEmtricitabineGenome, ViralGenomicsMacaca mulattaMutationRaltegravir PotassiumRNA, ViralSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusTenofovirViral LoadAnti-Retroviral AgentsDNA, ViralEmtricitabineRaltegravir PotassiumRNA, ViralTenofovirgenome intactnessgenomic integritypersistent viral reservoirsingle-genome sequencingSIV

Identifiers

PMID31597776
PMCPMC6912123
OpenAlexW2979447366

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.