Abstract:
:Human papillomavirus (HPV) infection of the genital tract is common; however, only about 10 to 15% of infections persist, and approximately 10 to 15% of these persistent infections result in cancer. Basal epidermal stem cells are the presumed target cells for HPV infection, providing a reservoir of latently infected cells that persist over time and initiate lesions. However, it is not known whether stem cell density has any influence on transformation of human keratinocytes by HPV. We explored the relationship between stem cell properties of normal human keratinocytes and their susceptibility to transformation by HPV16 DNA. Normal human keratinocyte isolates (NHKc) derived from different donors were cultured in three-dimensional anchorage-free suspension to assess their spheroid-forming ability. NHKc spheroids were then plated back into plastic monolayer culture and transfected with full-length HPV16 DNA, which we have previously shown to integrate into the host cell genome upon transfection. Spheroid-derived NHKc (SD-NHKc) and fluorescence-activated cell sorting-purified populations of basal stem-like keratinocytes, expressing low levels of epidermal growth factor receptor and high levels of integrin alpha 6 (EGFRlo/ITGα6hi), responded to transfection with HPV16 DNA with more vigorous proliferation, greater immortalization efficiency, and faster progression to differentiation resistance than autologous mass-cultured cells. Conversely, cells committed to terminal differentiation (EGFRhi/ITGα6lo) grew slowly after transfection with HPV16 and failed to generate immortalized or DR clones. HPV16 DNA induced stem cell properties in mass-cultured NHKc. We conclude that HPV16 preferentially immortalizes basal keratinocytes with stem cell properties and that these cells readily achieve a differentiation-resistant phenotype upon immortalization by HPV16.IMPORTANCE This paper explores the relationship between the stem cell properties of normal human epidermal cells in culture and these cells' susceptibility to transformation by HPV16 DNA, the HPV type present in about 50% of cervical cancers. We report variable susceptibilities to HPV16-mediated transformation among different keratinocyte isolates derived from neonatal foreskin. Our findings provide strong experimental evidence that HPV16 preferentially transforms basal keratinocytes with stem cell properties. Insights gained from these studies increase our understanding of the host cell-specific factors influencing individual susceptibility to HPV-driven transformation and the contributing factors leading to preneoplastic and neoplastic progression of HPV-positive lesions.
journal_name
J Viroljournal_title
Journal of virologyauthors
Woappi Y,Hosseinipour M,Creek KE,Pirisi Ldoi
10.1128/JVI.00331-18subject
Has Abstractpub_date
2018-05-14 00:00:00issue
11eissn
0022-538Xissn
1098-5514pii
JVI.00331-18journal_volume
92pub_type
杂志文章abstract::Interleukin-10 (IL-10) suppresses the maturation and cytokine production of dendritic cells (DCs), key regulators of adaptive immunity, and prevents the activation and polarization of naïve T cells towards protective gamma interferon-producing effectors. We hypothesized that human cytomegalovirus (HCMV) utilizes its v...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.16.8720-8731.2004
更新日期:2004-08-01 00:00:00
abstract::Hepatitis C virus (HCV) is a single-stranded positive-sense RNA hepatotropic virus. Despite cellular defenses, HCV is able to replicate in hepatocytes and to establish a chronic infection that could lead to severe complications and hepatocellular carcinoma. An important player in subverting the host response to HCV in...
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pub_type: 杂志文章
doi:10.1128/JVI.00880-17
更新日期:2017-08-24 00:00:00
abstract::Fanconi anemia (FA) patients have an increased risk for squamous cell carcinomas (SCCs) at sites of predilection for infection with high-risk human papillomavirus (HPV) types, including the oral cavity and the anogenital tract. We show here that activation of the FA pathway is a frequent event in cervical SCCs. We fou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01121-07
更新日期:2007-12-01 00:00:00
abstract::Infection with human T-cell leukemia virus type 1 (HTLV-1) can result in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disease of the central nervous system (CNS). HTLV-2 is highly related to HTLV-1 at the genetic level and shares a high degree of sequen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01513-06
更新日期:2007-02-01 00:00:00
abstract::Herpes simplex virus 1 (HSV-1) establishes a lifelong latent infection in peripheral nerve ganglia. Periodically, the virus reactivates from this latent reservoir and is transported to the original site of infection. Strains of HSV-1 have been noted to vary greatly in their virulence and reactivation efficiencies in a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00796-20
更新日期:2020-07-16 00:00:00
abstract::Treatment of cells with lectins specific for N-acetylglucosamine (GlcNAc) blocked infection by mouse cytomegalovirus (MCMV), and GlcNAc pretreatment of the lectin blocked this effect. MCMV failed to infect N-acetylglucosaminidase (GlcNAcase)-treated mouse embryo fibroblasts (MEF). GlcNAc and GlcNAc-containing syntheti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.11.5430-5440.1990
更新日期:1990-11-01 00:00:00
abstract::A double-isotopic label difference analysis of polyacrylamide gels has been used to distinguish between cellular and viral protein accumulation in infected cells and to quantify the kinetics of accumulation of viral polypeptides. This technique, coupled with the determination of total radioactive amino acid incorporat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.4.788-800.1974
更新日期:1974-04-01 00:00:00
abstract::Tegument is a unique structure of herpesvirus, which surrounds the capsid and interacts with the envelope. Morphogenesis of gammaherpesvirus is poorly understood due to lack of efficient lytic replication for Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8, which are etiologically as...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00497-09
更新日期:2009-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01126-15
更新日期:2015-10-01 00:00:00
abstract::The family Bunyaviridae is the most diversified family of RNA viruses. We describe a novel prototypic bunyavirus, tentatively named Gouléako virus, isolated from various mosquito species trapped in Côte d'Ivoire. The S segment comprised 1,087 nucleotides (nt), the M segment 3,188 nt, and the L segment 6,358 nt, consti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00230-11
更新日期:2011-09-01 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered human gamma herpesvirus strongly implicated in AIDS-related neoplasms. We report here the identification in the KSHV genome of a gene for a protein designated K-bZIP and belonging to the basic-leucine zipper (bZIP) family of transcription factors....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.3.1909-1917.1999
更新日期:1999-03-01 00:00:00
abstract::A novel species of 30S RNA has been detected in a variety of mouse cell lines. The 30S RNA is specifically packaged by helper-independent type C viruses propagated in such cells. Nucleic acid hybridization detects no homology between the 30SRNA and the genomic RNA of helper-independent mouse type C viruses. The proper...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.1.115-123.1978
更新日期:1978-01-01 00:00:00
abstract::Respiratory syncytial virus (RSV) infection of children previously immunized with a nonlive, formalin-inactivated (FI)-RSV vaccine has been associated with serious enhanced respiratory disease (ERD). Consequently, detailed studies of potential ERD are a critical step in the development of nonlive RSV vaccines targetin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02180-16
更新日期:2017-03-29 00:00:00
abstract::VP16-H is an essential structural protein of herpes simplex virus type 1 (HSV-1) and is also a potent activator of virus immediate-early (IE) gene expression. Current models of functional determinants within VP16-H indicate that it consists of two domains, an N-terminal domain involved in recruiting VP16-H to a multic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.21.10112-10121.2000
更新日期:2000-11-01 00:00:00
abstract::The intracellular assembly site for flaviviruses in currently not known but is presumed to be located within the lumen of the rough endoplasmic reticulum (RER). Building on previous studies involving immunofluorescence (IF) and cryoimmunoelectron microscopy of Kunjin virus (KUN)-infected cells, we sought to identify t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.22.10787-10799.2001
更新日期:2001-11-01 00:00:00
abstract::By using T1 oligonucleotide fingerprinting and mapping techniques, we analyzed the genomic structure of retroviruses produced by thymocytes and splenocytes of reciprocal bone marrow-and thymus-grafted chimeras. We found that the genetic factor(s) derived from NZB mice that suppresses the development of thymic leukemia...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.47.1.33-45.1983
更新日期:1983-07-01 00:00:00
abstract::The molecular basis of the temperature-sensitive (ts) phenotype of P3/Sabin, the type 3 vaccine strain of poliovirus, was investigated in light of the known correlation between ts and attenuation phenotypes. A phenylalanine at residue 91 of the capsid protein VP3 was a major determinant of both phenotypes, and attenua...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.10.5225-5231.1991
更新日期:1991-10-01 00:00:00
abstract::Particular interest in human T lymphocyte lymphoma/leukemia virus (HTLV) derives from the close association of HTLV with several types of human mature T lymphocyte malignancies and the strong possibility that HTLV is the causative agent of this group of leukemias and lymphomas. This is the first report to show that HT...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.2.440-446.1985
更新日期:1985-02-01 00:00:00
abstract::Extracts made from human respiratory syncytial virus (RSV)-infected Hep-2 cells synthesized mRNAs encoded by all known viral genes. In contrast, RSV ribonucleoproteins purified from infected cells failed to transcribe in vitro; transcription was restored by addition of a cytoplasmic extract of uninfected Hep-2 cells, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.11.6813-6818.1992
更新日期:1992-11-01 00:00:00
abstract::We have designed a ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in U5 (at nucleotide +115). This ribozyme was tested in vitro and was found to give efficient and specific digestion of RNA containing the HIV-1 U5 sequence. When the U5 ribozyme was placed into the HIV-1 genome, virus replication...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.3.1432-1441.1992
更新日期:1992-03-01 00:00:00
abstract::The herpes simplex virus (HSV) virion host shutoff (vhs) protein (UL41 gene product) is a component of the HSV virion tegument that triggers shutoff of host protein synthesis and accelerated mRNA degradation during the early stages of HSV infection. vhs displays weak amino acid sequence similarity to the fen-1 family ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9222-9231.1999
更新日期:1999-11-01 00:00:00
abstract::During lytic infection, the genome of herpes simplex virus 1 (HSV-1) is associated with limited levels of histones but does not form a regular repeating nucleosomal structure. However, the previous observation that chromatin remodeling factors are recruited into viral replication compartments indicates that chromatin ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01575-08
更新日期:2008-12-01 00:00:00
abstract::The E5 protein of human papillomavirus type 16 is a small, hydrophobic protein that localizes predominantly to membranes of the endoplasmic reticulum (ER). To define the orientation of E5 in these membranes, we employed a differential, detergent permeabilization technique that makes use of the ability of low concentra...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01968-09
更新日期:2010-02-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) particles typically contain small amounts of the surface envelope protein (SU), and this is widely believed to be due to shedding of SU from mature virions. We purified proteins from HIV-1 and SIV isolates using procedures which allow ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.11.5315-5325.2002
更新日期:2002-06-01 00:00:00
abstract::The human cytomegalovirus (HCMV) major immediate-early (MIE) enhancer contains five functional cyclic AMP (cAMP) response elements (CRE). Because the CRE in their native context do not contribute appreciably to MIE enhancer/promoter activity in lytically infected human fibroblasts and NTera2 (NT2)-derived neurons, we ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01524-06
更新日期:2007-06-01 00:00:00
abstract::The adenovirus E1A 243R oncoprotein is capable of transactivating the expression of the human proliferating cell nuclear antigen (PCNA) promoter. Mutational analysis of the E1A 243R protein suggested that both its p300/CBP- and p107-binding regions are required for optimal induction of the PCNA promoter (C. Kannabiran...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.2.1138-1145.1998
更新日期:1998-02-01 00:00:00
abstract::Cells that express glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) resist infection by HSV-1 and HSV-2 because of interference with viral penetration. The results presented here show that both HSV-1 and HSV-2 gD can mediate interference and that various HSV-1 and HSV-2 strains differ in sensitivity to this ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.8.5171-5176.1995
更新日期:1995-08-01 00:00:00
abstract::The major envelope glycoproteins gp120 and gp41 of human immunodeficiency virus type 1, the causative agent for human AIDS, contain numerous N-linked oligosaccharides. We report here our discovery that N-acetylglucosamine residues within the complex-type N-linked oligosaccharides of both gp120 and its precursor, gp160...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.2.943-952.1993
更新日期:1993-02-01 00:00:00
abstract:UNLABELLED:Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, and some molecules of this family also exhibit antiviral properties. Here we tested several derivatives of 4-aminoquinolines and piperazines for their activity against hepatitis C virus (HCV). We screened 11 molecul...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00404-16
更新日期:2016-09-12 00:00:00
abstract::The Middle East respiratory syndrome coronavirus (MERS-CoV) nonstructural protein 16 (nsp16) is an S-adenosyl-l-methionine (SAM)-dependent 2'-O-methyltransferase (2'-O-MTase) that is thought to methylate the ribose 2'-OH of the first transcribed nucleotide (N1) of viral RNA cap structures. This 2'-O-MTase activity is ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02217-16
更新日期:2017-02-14 00:00:00