Altered host range of HIV-1 after passage through various human cell types

Virology ◽  
1991 ◽  
Vol 181 (1) ◽  
pp. 288-294 ◽  
Author(s):  
Cecilia Cheng-Mayer ◽  
Deborah Seto ◽  
Jay A. Levy
Keyword(s):  
1989 ◽  
Vol 170 (4) ◽  
pp. 1149-1163 ◽  
Author(s):  
R Collman ◽  
N F Hassan ◽  
R Walker ◽  
B Godfrey ◽  
J Cutilli ◽  
...  

To characterize the host range of different strains of HIV-1, we have used four types of cells, primary monocyte-derived macrophages (MDM), primary PBL, a promonocyte cell line (U937), and a CD4+ T cell line (SUP-T1). These cells were infected with three prototype strains of HIV-1, a putative lymphocyte-tropic strain (IIIB), and two putative monocyte-tropic strains (SF162 and DV). Infections were monitored by assays for infectious virus, for cell-free and cell-associated viral antigen (p24), and for the proportion of cells infected by immunohistochemical staining. It was concluded that: (a) the use of four different cell types provides a useful biological matrix for distinguishing the tropism of different strains of HIV-1; this matrix yields more information than the infection of any single cell type. (b) A monocyte-tropic strain of HIV-1, such as strain SF162, shows a reciprocal host range when compared with a lymphocyte-tropic strain such as IIIB; strain SF162 replicates well in primary MDM but not in U937 or SUP-T1 cells, while strain IIIB replicates well in both U937 and SUP-T1 cells but not in MDM. (c) Both lymphocyte-tropic and monocyte-tropic strains of HIV-1 replicate well in PBL. (d) The promonocyte cell line, U937, and the T cell line, SUP-T1, differ markedly from primary cells, such as MDM and PBL, in their ability to support the replication of different strains of HIV-1; these cell lines cannot be used as surrogates for primary cells in host range studies of HIV-1 strains.


2001 ◽  
Vol 75 (17) ◽  
pp. 7944-7955 ◽  
Author(s):  
Noriko Nakajima ◽  
Richard Lu ◽  
Alan Engelman

ABSTRACT Functional retroviral integrase protein is thought to be essential for productive viral replication. Yet, previous studies differed on the extent to which integrase mutant viruses expressed human immunodeficiency virus type 1 (HIV-1) genes from unintegrated DNA. Although one reason for this difference was that class II integrase mutations pleiotropically affected the viral life cycle, another reason apparently depended on the identity of the infected cell. Here, we analyzed integrase mutant viral infectivities in a variety of cell types. Single-round infectivity of class I integration-specific mutant HIV-1 ranged from <0.03 to 0.3% of that of the wild type (WT) across four different T-cell lines. Based on this approximately 10-fold influence of cell type on mutant gene expression, we examined class I and class II mutant replication kinetics in seven different cell lines and two primary cell types. Unexpectedly, some cell lines supported productive class I mutant viral replication under conditions that restricted class II mutant growth. Cells were defined as permissive, semipermissive, or nonpermissive based on their ability to support the continual passage of class I integration-defective HIV-1. Mutant infectivity in semipermissive and permissive cells as quantified by 50% tissue culture infectious doses, however, was only 0.0006 to 0.005% of that of WT. Since the frequencies of mutant DNA recombination in these lines ranged from 0.023 to <0.093% of the WT, we conclude that productive replication in the absence of integrase function most likely required the illegitimate integration of HIV-1 into host chromosomes by cellular DNA recombination enzymes.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1235
Author(s):  
Leah D. Brandt ◽  
Shuang Guo ◽  
Kevin W. Joseph ◽  
Jana L. Jacobs ◽  
Asma Naqvi ◽  
...  

Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, termed repliclones. The digital droplet PCR assays commonly used to quantify intact proviruses do not differentiate among specific repliclones, thus the dynamics of repliclones are not well defined. The major challenge in tracking repliclones is the relative rarity of the cells carrying specific intact proviruses. To date, detection and accurate quantification of repliclones requires in-depth integration site sequencing. Here, we describe a simplified workflow using integration site-specific qPCR (IS-qPCR) to determine the frequencies of the proviruses integrated in individual repliclones. We designed IS-qPCR to determine the frequencies of repliclones and clones of cells that carry defective proviruses in samples from three donors. Comparing the results of IS-qPCR with deep integration site sequencing data showed that the two methods yielded concordant estimates of clone frequencies (r = 0.838). IS-qPCR is a potentially valuable tool that can be applied to multiple samples and cell types over time to measure the dynamics of individual repliclones and the efficacy of treatments designed to eliminate them.


2013 ◽  
Vol 87 (9) ◽  
pp. 5296-5299 ◽  
Author(s):  
C. M. Holtz ◽  
L. M. Mansky
Keyword(s):  

AIDS ◽  
1999 ◽  
Vol 13 (3) ◽  
pp. 333-339 ◽  
Author(s):  
Kamal El Messaoudi ◽  
Lise Thiry ◽  
Nicole Van Tieghem ◽  
Corinne Liesnard ◽  
Yvon Englert ◽  
...  

2009 ◽  
Vol 14 (9) ◽  
pp. 1054-1066 ◽  
Author(s):  
Keith A. Houck ◽  
David J. Dix ◽  
Richard S. Judson ◽  
Robert J. Kavlock ◽  
Jian Yang ◽  
...  

The complexity of human biology has made prediction of health effects as a consequence of exposure to environmental chemicals especially challenging. Complex cell systems, such as the Biologically Multiplexed Activity Profiling (BioMAP) primary, human, cell-based disease models, leverage cellular regulatory networks to detect and distinguish chemicals with a broad range of target mechanisms and biological processes relevant to human toxicity. Here the authors use the BioMAP human cell systems to characterize effects relevant to human tissue and inflammatory disease biology following exposure to the 320 environmental chemicals in the Environmental Protection Agency’s (EPA’s) ToxCast phase I library. The ToxCast chemicals were assayed at 4 concentrations in 8 BioMAP cell systems, with a total of 87 assay endpoints resulting in more than 100,000 data points. Within the context of the BioMAP database, ToxCast compounds could be classified based on their ability to cause overt cytotoxicity in primary human cell types or according to toxicity mechanism class derived from comparisons to activity profiles of BioMAP reference compounds. ToxCast chemicals with similarity to inducers of mitochondrial dysfunction, cAMP elevators, inhibitors of tubulin function, inducers of endoplasmic reticulum stress, or NFκB pathway inhibitors were identified based on this BioMAP analysis. This data set is being combined with additional ToxCast data sets for development of predictive toxicity models at the EPA. ( Journal of Biomolecular Screening 2009:1054-1066)


2009 ◽  
Vol 1 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Claire Dalmay ◽  
Arnaud Pothier ◽  
Mathilde Cheray ◽  
Fabrice Lalloue ◽  
Marie-Odile Jauberteau ◽  
...  

This paper presents an original biosensor chip allowing determination of intrinsic relative permittivity of biological cells at microwave frequencies. This sensor permits non-invasive cell identification and discrimination using an RF signal to probe intracellular medium of biological samples. Indeed, these sensors use an RF planar resonator that allows detection capabilities on less than 10 cells, thanks to the microscopic size of its sensitive area. Especially, measurements between 15 and 35 GHz show the ability label-free biosensors to differentiate two human cell types using their own electromagnetic characteristics. The real part of permittivity of cells changes from 20 to 48 for the nervous system cell types studied. The proposed biodetection method is detailed and we show how the accuracy and the repeatability of measurements have been improved to reach reproducible measurements.


2020 ◽  
Author(s):  
Feng Tian ◽  
Fan Zhou ◽  
Xiang Li ◽  
Wenping Ma ◽  
Honggui Wu ◽  
...  

SummaryBy circumventing cellular heterogeneity, single cell omics have now been widely utilized for cell typing in human tissues, culminating with the undertaking of human cell atlas aimed at characterizing all human cell types. However, more important are the probing of gene regulatory networks, underlying chromatin architecture and critical transcription factors for each cell type. Here we report the Genomic Architecture of Cells in Tissues (GeACT), a comprehensive genomic data base that collectively address the above needs with the goal of understanding the functional genome in action. GeACT was made possible by our novel single-cell RNA-seq (MALBAC-DT) and ATAC-seq (METATAC) methods of high detectability and precision. We exemplified GeACT by first studying representative organs in human mid-gestation fetus. In particular, correlated gene modules (CGMs) are observed and found to be cell-type-dependent. We linked gene expression profiles to the underlying chromatin states, and found the key transcription factors for representative CGMs.HighlightsGenomic Architecture of Cells in Tissues (GeACT) data for human mid-gestation fetusDetermining correlated gene modules (CGMs) in different cell types by MALBAC-DTMeasuring chromatin open regions in single cells with high detectability by METATACIntegrating transcriptomics and chromatin accessibility to reveal key TFs for a CGM


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