scholarly journals Mesenchymal Stromal Cells: a Possible Reservoir for HIV-1?

2022 ◽  
Author(s):  
K. Kallmeyer ◽  
M. A. Ryder ◽  
M. S. Pepper
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
The Body ◽  
Differentiation Potential ◽  
Proliferation Capacity ◽  
Highly Active ◽  
Latent Hiv ◽  
Hiv 1

AbstractThe introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV)-1 into a chronic, well-managed disease. However, these therapies do not eliminate all infected cells from the body despite suppressing viral load. Viral rebound is largely due to the presence of cellular reservoirs which support long-term persistence of HIV-1. A thorough understanding of the HIV-1 reservoir will facilitate the development of new strategies leading to its detection, reduction, and elimination, ultimately leading to curative therapies for HIV-1. Although immune cells derived from lymphoid and myeloid progenitors have been thoroughly studied as HIV-1 reservoirs, few studies have examined whether mesenchymal stromal/stem cells (MSCs) can assume this function. In this review, we evaluate published studies which have assessed whether MSCs contribute to the HIV-1 reservoir. MSCs have been found to express the receptors and co-receptors required for HIV-1 entry, albeit at levels of expression and receptor localisation that vary considerably between studies. Exposure to HIV-1 and HIV-1 proteins alters MSC properties in vitro, including their proliferation capacity and differentiation potential. However, in vitro and in vivo experiments investigating whether MSCs can become infected with and harbour latent integrated proviral DNA are lacking. In conclusion, MSCs appear to have the potential to contribute to the HIV-1 reservoir. However, further studies are needed using techniques such as those used to prove that cluster of differentiation (CD)4+ T cells constitute an HIV-1 reservoir before a reservoir function can definitively be ascribed to MSCs. Graphical abstract MSCs may contribute to HIV-1 persistence in vivo in the vasculature, adipose tissue, and bone marrow by being a reservoir for latent HIV-1. To harbour latent HIV-1, MSCs must express HIV-1 entry markers, and show evidence of productive or latent HIV-1 infection. The effect of HIV-1 or HIV-1 proteins on MSC properties may also be indicative of HIV-1 infection.

scholarly journals Mutations in HIV-1gagandpolCompensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease

2012 ◽  
Vol 56 (8) ◽  
pp. 4320-4330 ◽  
Author(s):  
Milan Kožíšek ◽  
Sandra Henke ◽  
Klára Grantz Šašková ◽  
Graeme Brendon Jacobs ◽  
Anita Schuch ◽  
...  
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Viral Fitness ◽  
Drug Pressure ◽  
Viral Loads ◽  
Highly Active ◽  
Subtype B ◽  
Hiv 1

ABSTRACTDuring the last few decades, the treatment of HIV-infected patients by highly active antiretroviral therapy, including protease inhibitors (PIs), has become standard. Here, we present results of analysis of a patient-derived, multiresistant HIV-1 CRF02_AG recombinant strain with a highly mutated protease (PR) coding sequence, where up to 19 coding mutations have accumulated in the PR. The results of biochemical analysisin vitroshowed that the patient-derived PR is highly resistant to most of the currently used PIs and that it also exhibits very poor catalytic activity. Determination of the crystal structure revealed prominent changes in the flap elbow region and S1/S1′ active site subsites. While viral loads in the patient were found to be high, the insertion of the patient-derived PR into a HIV-1 subtype B backbone resulted in reduction of infectivity by 3 orders of magnitude. Fitness compensation was not achieved by elevated polymerase (Pol) expression, but the introduction of patient-derivedgagandpolsequences in a CRF02_AG backbone rescued viral infectivity to near wild-type (wt) levels. The mutations that accumulated in the vicinity of the processing sites spanning the p2/NC, NC/p1, and p6pol/PR proteins lead to much more efficient hydrolysis of corresponding peptides by patient-derived PR in comparison to the wt enzyme. This indicates a very efficient coevolution of enzyme and substrate maintaining high viral loadsin vivounder constant drug pressure.

Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy

AIDS ◽  
2001 ◽  
Vol 15 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Secondo Sonza ◽  
Helen P. Mutimer ◽  
Robert Oelrichs ◽  
Darren Jardine ◽  
Katya Harvey ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Highly Active ◽  
Latent Hiv ◽  
Hiv 1

Could low level laser therapy and highly active antiretroviral therapy lead to complete eradication of HIV-1 in vitro?

2017 ◽  
Author(s):  
Masixole Yvonne Lugongolo ◽  
Sello Lebohang Manoto ◽  
Saturnin Ombinda-Lemboumba ◽  
Malik Maaza ◽  
Patience Mthunzi-Kufa
Keyword(s):  
Antiretroviral Therapy ◽  
Laser Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Low Level Laser Therapy ◽  
Complete Eradication ◽  
Low Level Laser ◽  
Highly Active ◽  
Level Laser ◽  
Hiv 1

scholarly journals Recovery of Replication-Competent Residual HIV-1 from Plasma of a Patient Receiving Prolonged, Suppressive Highly Active Antiretroviral Therapy

2010 ◽  
Vol 84 (16) ◽  
pp. 8348-8352 ◽  
Author(s):  
Gautam K. Sahu ◽  
Juan C. Sarria ◽  
Miles W. Cloyd
Keyword(s):  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Host Cells ◽  
Drug Resistant ◽  
Residual Viremia ◽  
Viral Genomes ◽  
Highly Active ◽  
Hiv 1 ◽  
Adherence To Therapy

ABSTRACT The clinical significance of persistent residual viremia in patients on prolonged highly active antiretroviral therapy (HAART) is not clear. Moreover, it remains to be demonstrated whether residual viremia consists of viruses capable of spreading infection in vivo upon termination of therapy. Using residual viral RNAs (vRNAs) isolated from a HAART-treated patient's plasma, we cloned full-length viral genomes and found that most of them could produce infectious, replication-competent HIVs when transfected into TZM-bl cells, suggesting that residual viruses produced in the absence of therapy can initiate fresh cycles of infection and spread in host cells. The data further indicate that residual viremia may pose a major concern with regard to the emergence of drug-resistant HIVs during periods of low adherence to therapy.

scholarly journals Evidence for Human Immunodeficiency Virus Type 1 Replication In Vivo in CD14+ Monocytes and Its Potential Role as a Source of Virus in Patients on Highly Active Antiretroviral Therapy

2002 ◽  
Vol 76 (2) ◽  
pp. 707-716 ◽  
Author(s):  
Tuofu Zhu ◽  
David Muthui ◽  
Sarah Holte ◽  
David Nickle ◽  
Feng Feng ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Highly Active Antiretroviral Therapy ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT In vitro studies show that human immunodeficiency virus type 1 (HIV-1) does not replicate in freshly isolated monocytes unless monocytes differentiate to monocyte-derived macrophages. Similarly, HIV-1 may replicate in macrophages in vivo, whereas it is unclear whether blood monocytes are permissive to productive infection with HIV-1. We investigated HIV-1 replication in CD14+ monocytes and resting and activated CD4+ T cells by measuring the levels of cell-associated viral DNA and mRNA and the genetic evolution of HIV-1 in seven acutely infected patients whose plasma viremia had been <100 copies/ml for 803 to 1,544 days during highly active antiretroviral therapy (HAART). HIV-1 DNA was detected in CD14+ monocytes as well as in activated and resting CD4+ T cells throughout the course of study. While significant variation in the decay slopes of HIV-1 DNA was seen among individual patients, viral decay in CD14+ monocytes was on average slower than that in activated and resting CD4+ T cells. Measurements of HIV-1 sequence evolution and the concentrations of unspliced and multiply spliced mRNA provided evidence of ongoing HIV-1 replication, more pronounced in CD14+ monocytes than in resting CD4+ T cells. Phylogenetic analyses of HIV-1 sequences indicated that after prolonged HAART, viral populations related or identical to those found only in CD14+ monocytes were seen in plasma from three of the seven patients. In the other four patients, HIV-1 sequences in plasma and the three cell populations were identical. CD14+ monocytes appear to be one of the potential in vivo sources of HIV-1 in patients receiving HAART.

Sign in / Sign up

Export Citation Format

Share Document