Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy

HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we g...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2017-05, Vol.13 (5), p.e1006359-e1006359
Main Authors: Fennessey, Christine M, Pinkevych, Mykola, Immonen, Taina T, Reynaldi, Arnold, Venturi, Vanessa, Nadella, Priyanka, Reid, Carolyn, Newman, Laura, Lipkey, Leslie, Oswald, Kelli, Bosche, William J, Trivett, Matthew T, Ohlen, Claes, Ott, David E, Estes, Jacob D, Del Prete, Gregory Q, Lifson, Jeffrey D, Davenport, Miles P, Keele, Brandon F
Format: Article
Language:English
Subjects:
Abundance
Acquired immune deficiency syndrome
Activation
AIDS
Animals
Anti-Retroviral Agents - therapeutic use
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Bar codes
Biology and Life Sciences
Biomedical research
Cancer
CD4 antigen
CD4-Positive T-Lymphocytes - virology
Drug therapy
Dynamic tests
Enumeration
Gene sequencing
Genes
Genetic distance
Genetic Markers - genetics
Genetic Variation
Genome, Viral - genetics
Growth rate
HIV
Human immunodeficiency virus
In vitro methods and tests
Infections
Infectious diseases
Inoculation
Interruption
Intravenous administration
Laboratories
Latency
Latent infection
Lymphocytes
Lymphocytes T
Macaca mulatta
Male
Mathematical analysis
Medical research
Medicine and Health Sciences
Models, Theoretical
Monkeys
Parameter estimation
Plasma
Primates
Relative abundance
Replication
Research and Analysis Methods
Sequence Analysis, DNA
Simian Acquired Immunodeficiency Syndrome - drug therapy
Simian Acquired Immunodeficiency Syndrome - virology
Simian immunodeficiency virus
Simian Immunodeficiency Virus - drug effects
Simian Immunodeficiency Virus - genetics
Simian Immunodeficiency Virus - physiology
Studies
Therapy
Transcription
Viral Load
Viremia
Virus Replication
Viruses
Vpr protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M) with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART) for 82 days starting on day 6 post-infection (study 1). Plasma viremia was reduced from >106 to
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1006359