Intact and defective proviruses proviruses. Medical search. Frequent questions

Although HIV infection can be suppressed by antiretroviral therapy (ART), latent HIV-1 proviruses persist in the genomes of long-lived CD4+ T cells in people living with HIV 1 , 2 . (nature.com)
Twenty-five of the 213 non-induced isolates, when sequenced, had fully intact genomes when compared to those that did reactivate. (hopkinsmedicine.org)
The researchers utilized the intact proviral DNA assay (IPDA), which distinguishes between intact and defective proviruses genomes. (cbirt.net)
Intact HIV genomes represent 2% and 25% of all proviruses in the two participants, and are mainly detected in secondary lymphoid organs, with the spleen and mediastinal lymph nodes harboring intact viral genomes in both individuals. (mendeley.com)
Her finding presents an obstacle to anti-retroviral therapies currently used to treat HIV infection, which only target actively replicating virus rather than those proviruses laying dormant in host genomes, which have the potential to reseed infection. (wikipedia.org)
An intrinsic limitation of these assays is the fact that while the production of ca-RNA reflects transcriptionally competent provirus, it also detects defective genomes that can be partially or entirely transcribed. (biomedcentral.com)
Analysis of 213 noninduced proviral clones from treated patients showed 88.3% with identifiable defects but 11.7% with intact genomes and normal long terminal repeat (LTR) function. (wustl.edu)

These findings suggest that infected cells harboring either intact or defective proviruses expand, migrate, and possibly circulate between anatomical sites. (mendeley.com)

The hidden HIV, researchers say, is part of the so-called latent reservoir of functional proviruses that remains long after antiretroviral drug therapy has successfully brought viral replication to a standstill. (hopkinsmedicine.org)
The disappointing finding comes after a three-year series of lab experiments, which they say represents the most detailed and comprehensive analysis to date of the latent reservoir of HIV proviruses. (hopkinsmedicine.org)
Senior study investigator Robert Siliciano, M.D., Ph.D., who in 1995 first showed that reservoirs of dormant HIV were present in immune cells, says that while the latest study results show most proviruses in the latent reservoir are defective, curing the disease will depend on finding a way to target all proviruses with the potential to restart the infection. (hopkinsmedicine.org)
Lead study investigator and Johns Hopkins postdoctoral fellow Ya-Chi Ho, M.D., Ph.D., says the team's investigation of "the true size" of the latent reservoir was prompted by a large discrepancy between the two established techniques for measuring how much provirus is in immune system cells. (hopkinsmedicine.org)
The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4(+) T cells that remain relatively quiescent. (nih.gov)
As a result, the latent reservoir has largely been thought to be defective. (wikipedia.org)
Using a combination of molecular and genetic techniques, however, Ho found that the latent HIV provirus reservoir persists at much higher levels than previously believed. (wikipedia.org)
During that time, she continued to characterize proviruses in the latent reservoir. (wikipedia.org)
These are the quickest and easiest assays to measure the frequency of HIV-infected cells, but they largely overestimate the size of the reservoir by detecting defective proviruses [ 1 ]. (biomedcentral.com)
The identification of replication-competent noninduced proviruses indicates that the size of the latent reservoir - and, hence, the barrier to cure - may be up to 60-fold greater than previously estimated. (wustl.edu)

Siliciano says that all of these non-induced proviruses had previously been thought to be defective, with no possible role in resumption of the disease. (hopkinsmedicine.org)
Previously, these mutant proviruses were thought to be defective and therefore harmless, but Ho and her colleagues demonstrated that at least some of these mutants produce proteins the host immune system recognizes as HIV. (wikipedia.org)

When assayed by VOA, the relative distribution of clones is definitely dynamic in that the number of cells that reactivate a specific latent provirus regularly differs between time points (17, 22). (koeki-data.org)
When host T cells are activated, the latent provirus can become induced to release active virus, though the vast majority of them do not due to mutation events while incorporated in the host genome. (wikipedia.org)

Most proviruses persisting in people living with HIV (PWH) on antiretroviral therapy (ART) are defective. (nature.com)
If antiretroviral therapy is stopped or interrupted, some proviruses can reactivate, allowing HIV to make copies of itself and resume infection of other immune cells. (hopkinsmedicine.org)
That approach refers to forcing dormant proviruses to "turn back on," making them "visible" and vulnerable to the immune system's cytolytic "killer" T cells, and then eliminating every last infected cell from the body while antiretroviral drugs prevent any new cells from becoming infected. (hopkinsmedicine.org)
Antiretroviral therapy fails to cure HIV-1 infection because latent proviruses persist in resting CD4 + T cells. (wustl.edu)

HIV-1 proviruses can persist during ART in clonally-expanded populations of CD4+ T cells. (frontiersin.org)

These findings show that the vast majority of HIV-1 proviruses within expanded T cell clones, including intact proviruses, may be transcriptionally silent at any given time, implying that infected T cells may be able to be activated to proliferate without inducing the expression of the integrated provirus or, alternatelively, may be able to proliferate without cellular activation. (frontiersin.org)

The size of the pool of cells carrying replication-competent HIV is largely overestimated by DNA assays, as a result of a large proportion of defective viruses, and underestimated by co-culture outgrowth assays. (biomedcentral.com)
The mechanism by which latent viruses, such as genetically transmitted tumor viruses ( PROVIRUSES ) or PROPHAGES of lysogenic bacteria, are induced to replicate and then released as infectious viruses. (lookformedical.com)

We evaluated the same samples from 10 male PWH on ART using the two-probe intact proviral DNA assay (IPDA) and near full length (nfl) Q4PCR. (nature.com)
For example, the intact proviral DNA assay (IPDA) 17 targets the HIV-1 Packaging Signal (Ψ) and the Envelope/Rev Responsive Element (RRE). (nature.com)

She says the team's original method of calculating only reactivated proviruses yielded numbers that were 300-fold lower than a DNA-based technique used to gauge how many total proviral copies, both dormant and reactivated, are present. (hopkinsmedicine.org)

However, higher fractions and levels of RNA were found in cells with proviruses containing multiple drug resistance mutations, including those contributing to rebound viremia. (frontiersin.org)
Analysis of the remaining (88 percent of) non-induced proviruses showed that all were defective, possessing genetic deletions and mutations that would forestall viral replication. (hopkinsmedicine.org)
During evolution, most ERVs have accumulated mutations that rendered them defective and unable to produce infectious viral particles. (gla.ac.uk)

Both assays admitted similar ratios of intact to total HIV DNA, but IPDA found ~40-fold more intact proviruses. (nature.com)
We conclude that sensitive multi-probe assays combined with specific nfl-verified assays would be optimal to document absolute and changing levels of intact HIV proviruses. (nature.com)
These assays designate proviral DNA as intact or defective based on hybridization of PCR-amplified proviral DNA to probes in two to five relatively conserved locations on the HIV-1 genome. (nature.com)

To date, few examples of an expanded clones containing replication-competent proviruses exist, although it is suspected to be common. (frontiersin.org)
To address this question, we determined the fraction of HIV-1 proviruses within the AMBI-1 clone that expresses unspliced cell-associated RNA during ART and compared this fraction to 33 other infected T cell clones within the same individual. (frontiersin.org)
The fraction of cells within clones that contained HIV-1 RNA was not different in clones with intact (median 2.3%) versus defective (median 3.5%) proviruses ( p = 0.2). (frontiersin.org)
However, none of the 75 expanded T cell clones assayed contained intact virus. (nih.gov)
Using direct sequencing and genome synthesis, we reconstructed full-length intact noninduced proviral clones and demonstrated growth kinetics comparable to reconstructed induced proviruses from the same patients. (wustl.edu)

Rabbit Polyclonal to IRAK2 a near full-size HIV-1 genome is definitely expected because a portion of defective proviruses retains undamaged (21). (koeki-data.org)
Finally, sequence analyses revealed that the domestic sheep has acquired, by genome amplification, several copies of the enJS56A1 provirus, reinforcing the hypothesis that this locus has provided an evolutionary advantage to the host. (gla.ac.uk)
A) When a latently infected cell is super-infected with a helper virus, such adenovirus or herpes x virus , the AAV gene expression program is activated leading to the AAV Rep-mediated rescue (i.e., excision) of the provirus DNA from the host cell chromosome, followed by replication and packaging of the viral genome. (icpcovid.com)

Further lab experiments on the cloned proviruses showed that the intact, non-induced proviruses could be reconstructed to produce active virus, which in turn could replicate in human immune cells. (hopkinsmedicine.org)

was also a source of persistent viremia on ART, begging the question of how the AMBI-1 clone can survive despite infection with a replication-competent, actively-expressing provirus. (frontiersin.org)
Study results showed that among 213 HIV proviruses isolated from the reservoirs of eight patients and initially unresponsive to highly potent biological stimuli, some 12 percent could later still become active, and were capable of replicating their genetic material and transmitting infection to other cells. (hopkinsmedicine.org)

The barrier to curing HIV-1 is thought to reside primarily in CD4(+) T cells containing silent proviruses. (nih.gov)
Few of the fast decaying first-phase cells were found in circulating CD4+ T cells with intact proviruses. (cbirt.net)
Her research is supported by a National Institutes of Health R01 Research Grant awarded through the National Institute of Allergy and Infectious Diseases to study the clonal expansion of HIV-infected T cells, which can contribute to viral rebound if T cells containing intact provirus are activated, presenting an obstacle to HIV treatment. (wikipedia.org)
The intermittent but prolonged detection of this replication-defective HIV variant in the patient′s plasma among other viral populations strongly suggests that this variant is released from highly stable productively infected cells present in vivo during therapy. (biomedcentral.com)
What seems less well known is that inserted provirus in non-cancerous breast cells also has a negative regulatory element. (phoenixrising.me)

1% of proviruses are induced to release infectious virus after maximum in vitro activation. (wustl.edu)

However, the mean intact half-lives were different: 108 months for IPDA and 65 months for Q4PCR. (nature.com)
To reconcile this difference, we modeled additional longitudinal IPDA data and showed that decelerating intact decay could arise from very long-lived intact proviruses and/or misclassified defective proviruses: slowly decaying defective proviruses that are intact in IPDA probe locations (estimated up to 5%, in agreement with sequence library based predictions). (nature.com)

However, rarer intact proviruses almost always reinitiate viral rebound if ART stops. (nature.com)
Therefore, assessing therapies to prevent viral rebound hinges on specifically quantifying intact proviruses. (nature.com)

Some ERVs, however, have maintained intact open reading frames for some of their genes, and have been co-opted by the host as they fulfil important biological functions. (gla.ac.uk)
So far, the approved AAV-based drugs and most clinical trials utilizing AAV vectors aim to supplement a defective gene with a new, working copy [ 3 ], but many studies have investigated AAV for the delivery of non-self therapeutic genes. (biomedcentral.com)

She found that proteins derived from mutant proviruses upon CD4+ T cell activation elicit an immune response from cytotoxic T cell. (wikipedia.org)

In the latest study, researchers sequenced, or spelled out, the entire genetic code of HIV proviruses that reactivated and those that could not be induced to do so. (hopkinsmedicine.org)

Most of these sequences qualify as junk but they are littered with defective transposable elements that are already included in the calculation of junk DNA. (blogspot.com)

The degradation of two-long-terminal repeat (2LTR) circles follows the same rapid and slow phases as intact proviruses, ruling out their use as a simple indicator of continuing viral replication. (cbirt.net)
During evolution, one of these enJSRV loci, enJS56A1, has acquired a defective and transdominant Gag polyprotein that blocks the late replication steps of related retroviruses, by a mechanism known as JSRV late restriction (JLR). (gla.ac.uk)

the integrated virus is known as a provirus. (wikipedia.org)

A mouse model of heart-specific defective mtThrRS editing was established. (cnrs.fr)

Ho has an additional R61 grant from NIH's National Institute on Drug Abuse to understand how medication-assisted treatment for opioid use disorder impacts the reactivation of HIV provirus for those infected with HIV to reduce the likelihood of reseeding illness. (wikipedia.org)

The model also demonstrates how misclassification can lead to underestimated efficacy of therapies that exclusively reduce intact proviruses. (nature.com)

Stereotaxic guided deletion of ERα in the arcuate nucleus increases bone mass in intact and ovariectomized females, confirming the central role of estrogen signaling in this sex-dependent bone phenotype. (regenerativemedicine.net)

If both regions are amplified within a single provirus, the sequence is said to be intact, and if only one of the two probes is positive the provirus is determined to be defective 17 . (nature.com)

Anatomy1

Organisms23

Diseases9

Chemicals and Drugs9

Analytical, Diagnostic and Therapeutic Techniques and Equipment5

Phenomena and Processes22

Information Science3

Genomes7

Either intact or defective proviruses1

Reservoir10

Thought to be defective2

Latent provirus2

Antiretroviral4

Persist1

Transcriptionally1

Viruses2

Proviral DNA assay2

Dormant1

Mutations3

Assays3

Clones5

Genome3

Replicate1

Infection2

Cells5

Infectious1

IPDA2

Viral rebound2

Genes2

Immune1

Genetic1

Sequences1

Replication2

Virus1

Specific1

Drug1

Reduce1

Role1

Single1