Assays to Measure Latency, Reservoirs, and Reactivation

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

HIV-1 persists even in patients who are successfully treated with combination antiretroviral therapy. The major barrier to cure is a small pool of latently infected resting CD4+ T cells carrying an integrated copy of the viral genome that is not expressed while the cells remain in a resting state. Targeting this latent reservoir is a major focus of HIV-1 cure research, and the development of a rapid and scalable assay for the reservoir is a rate-limiting step in the search for a cure. The most commonly used assays are standard PCR assays targeting conserved regions of the HIV-1 genome. However, because the vast majority of HIV-1 proviruses are defective, such assays may not accurately capture changes in the minor subset of proviruses that are replication-competent and that pose a barrier to cure. On the other hand, the viral outgrowth assay that was used to initially define the latent reservoir may underestimate reservoir size because not all replication-competent proviruses are induced by a single round of T cell activation in this assay. Therefore, this assay is best regarded as a definitive minimal estimate of reservoir size. The best approach may be to measure all of the proviruses with the potential to cause viral rebound. A variety of novel assays have recently been described. Ultimately, the assay that best predicts time to viral rebound will be the most useful to the cure effort.

Original languageEnglish (US)
Title of host publicationCurrent Topics in Microbiology and Immunology
PublisherSpringer Verlag
Pages23-41
Number of pages19
DOIs
StatePublished - Jan 1 2018

Publication series

NameCurrent Topics in Microbiology and Immunology
Volume417
ISSN (Print)0070-217X
ISSN (Electronic)2196-9965

Fingerprint

Proviruses
HIV-1
T-Lymphocytes
Viral Genome
Genome
Polymerase Chain Reaction
Research
Therapeutics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)

Cite this

Siliciano, J. M., & Siliciano, R. F. (2018). Assays to Measure Latency, Reservoirs, and Reactivation. In Current Topics in Microbiology and Immunology (pp. 23-41). (Current Topics in Microbiology and Immunology; Vol. 417). Springer Verlag. https://doi.org/10.1007/82_2017_75

Assays to Measure Latency, Reservoirs, and Reactivation. / Siliciano, Janet M; Siliciano, Robert F.

Current Topics in Microbiology and Immunology. Springer Verlag, 2018. p. 23-41 (Current Topics in Microbiology and Immunology; Vol. 417).

Research output: Chapter in Book/Report/Conference proceedingChapter

Siliciano, JM & Siliciano, RF 2018, Assays to Measure Latency, Reservoirs, and Reactivation. in Current Topics in Microbiology and Immunology. Current Topics in Microbiology and Immunology, vol. 417, Springer Verlag, pp. 23-41. https://doi.org/10.1007/82_2017_75
Siliciano JM, Siliciano RF. Assays to Measure Latency, Reservoirs, and Reactivation. In Current Topics in Microbiology and Immunology. Springer Verlag. 2018. p. 23-41. (Current Topics in Microbiology and Immunology). https://doi.org/10.1007/82_2017_75
Siliciano, Janet M ; Siliciano, Robert F. / Assays to Measure Latency, Reservoirs, and Reactivation. Current Topics in Microbiology and Immunology. Springer Verlag, 2018. pp. 23-41 (Current Topics in Microbiology and Immunology).
@inbook{25107772320f42f58276dce8bdf10941,
title = "Assays to Measure Latency, Reservoirs, and Reactivation",
abstract = "HIV-1 persists even in patients who are successfully treated with combination antiretroviral therapy. The major barrier to cure is a small pool of latently infected resting CD4+ T cells carrying an integrated copy of the viral genome that is not expressed while the cells remain in a resting state. Targeting this latent reservoir is a major focus of HIV-1 cure research, and the development of a rapid and scalable assay for the reservoir is a rate-limiting step in the search for a cure. The most commonly used assays are standard PCR assays targeting conserved regions of the HIV-1 genome. However, because the vast majority of HIV-1 proviruses are defective, such assays may not accurately capture changes in the minor subset of proviruses that are replication-competent and that pose a barrier to cure. On the other hand, the viral outgrowth assay that was used to initially define the latent reservoir may underestimate reservoir size because not all replication-competent proviruses are induced by a single round of T cell activation in this assay. Therefore, this assay is best regarded as a definitive minimal estimate of reservoir size. The best approach may be to measure all of the proviruses with the potential to cause viral rebound. A variety of novel assays have recently been described. Ultimately, the assay that best predicts time to viral rebound will be the most useful to the cure effort.",
author = "Siliciano, {Janet M} and Siliciano, {Robert F}",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/82_2017_75",
language = "English (US)",
series = "Current Topics in Microbiology and Immunology",
publisher = "Springer Verlag",
pages = "23--41",
booktitle = "Current Topics in Microbiology and Immunology",

}

TY - CHAP

T1 - Assays to Measure Latency, Reservoirs, and Reactivation

AU - Siliciano, Janet M

AU - Siliciano, Robert F

PY - 2018/1/1

Y1 - 2018/1/1

N2 - HIV-1 persists even in patients who are successfully treated with combination antiretroviral therapy. The major barrier to cure is a small pool of latently infected resting CD4+ T cells carrying an integrated copy of the viral genome that is not expressed while the cells remain in a resting state. Targeting this latent reservoir is a major focus of HIV-1 cure research, and the development of a rapid and scalable assay for the reservoir is a rate-limiting step in the search for a cure. The most commonly used assays are standard PCR assays targeting conserved regions of the HIV-1 genome. However, because the vast majority of HIV-1 proviruses are defective, such assays may not accurately capture changes in the minor subset of proviruses that are replication-competent and that pose a barrier to cure. On the other hand, the viral outgrowth assay that was used to initially define the latent reservoir may underestimate reservoir size because not all replication-competent proviruses are induced by a single round of T cell activation in this assay. Therefore, this assay is best regarded as a definitive minimal estimate of reservoir size. The best approach may be to measure all of the proviruses with the potential to cause viral rebound. A variety of novel assays have recently been described. Ultimately, the assay that best predicts time to viral rebound will be the most useful to the cure effort.

AB - HIV-1 persists even in patients who are successfully treated with combination antiretroviral therapy. The major barrier to cure is a small pool of latently infected resting CD4+ T cells carrying an integrated copy of the viral genome that is not expressed while the cells remain in a resting state. Targeting this latent reservoir is a major focus of HIV-1 cure research, and the development of a rapid and scalable assay for the reservoir is a rate-limiting step in the search for a cure. The most commonly used assays are standard PCR assays targeting conserved regions of the HIV-1 genome. However, because the vast majority of HIV-1 proviruses are defective, such assays may not accurately capture changes in the minor subset of proviruses that are replication-competent and that pose a barrier to cure. On the other hand, the viral outgrowth assay that was used to initially define the latent reservoir may underestimate reservoir size because not all replication-competent proviruses are induced by a single round of T cell activation in this assay. Therefore, this assay is best regarded as a definitive minimal estimate of reservoir size. The best approach may be to measure all of the proviruses with the potential to cause viral rebound. A variety of novel assays have recently been described. Ultimately, the assay that best predicts time to viral rebound will be the most useful to the cure effort.

UR - http://www.scopus.com/inward/record.url?scp=85049865516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049865516&partnerID=8YFLogxK

U2 - 10.1007/82_2017_75

DO - 10.1007/82_2017_75

M3 - Chapter

C2 - 29071475

AN - SCOPUS:85049865516

T3 - Current Topics in Microbiology and Immunology

SP - 23

EP - 41

BT - Current Topics in Microbiology and Immunology

PB - Springer Verlag

ER -