scholarly journals Extracellular Vesicles from Infected Cells Are Released Prior to Virion Release

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 781
Author(s):  
Yuriy Kim ◽  
Gifty A. Mensah ◽  
Sarah Al Sharif ◽  
Daniel O. Pinto ◽  
Heather Branscome ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Viral Proteins ◽  
Extracellular Vesicle ◽  
Virion Release ◽  
Human T Cell ◽  
Rich Media ◽  
T Cell Leukemia Virus ◽  
Infected Cells ◽  
Related Proteins ◽  
Hiv 1

Here, we have attempted to address the timing of EV and virion release from virally infected cells. Uninfected (CEM), HIV-1-infected (J1.1), and human T cell leukemia virus-1 (HTLV-1)-infected (HUT102) cells were synchronized in G0. Viral latency was reversed by increasing gene expression with the addition of serum-rich media and inducers. Supernatants and cell pellets were collected post-induction at different timepoints and assayed for extracellular vesicle (EV) and autophagy markers; and for viral proteins and RNAs. Tetraspanins and autophagy-related proteins were found to be differentially secreted in HIV-1- and HTLV-1-infected cells when compared with uninfected controls. HIV-1 proteins were present at 6 h and their production increased up to 24 h. HTLV-1 proteins peaked at 6 h and plateaued. HIV-1 and HTLV-1 RNA production correlated with viral protein expression. Nanoparticle tracking analysis (NTA) showed increase of EV concentration over time in both uninfected and infected samples. Finally, the HIV-1 supernatant from the 6-h samples was found not to be infectious; however, the virus from the 24-h samples was successfully rescued and infectious. Overall, our data indicate that EV release may occur prior to viral release from infected cells, thereby implicating a potentially significant effect of EVs on uninfected recipient cells prior to subsequent viral infection and spread.

scholarly journals The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jafar Rezaie ◽  
Cynthia Aslan ◽  
Mahdi Ahmadi ◽  
Naime Majidi Zolbanin ◽  
Fatah Kashanchi ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Biological Fluids ◽  
Recipient Cell ◽  
Leukemia Virus ◽  
Target Cells ◽  
Modern Approach ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells ◽  
Hiv 1

AbstractEukaryotic cells produce extracellular vesicles (EVs) mediating intercellular communication. These vesicles encompass many bio-molecules such as proteins, nucleic acids, and lipids that are transported between cells and regulate pathophysiological actions in the recipient cell. Exosomes originate from multivesicular bodies inside cells and microvesicles shed from the plasma membrane and participate in various pathological conditions. Retroviruses such as Human Immunodeficiency Virus -type 1 (HIV-1) and Human T-cell leukemia virus (HTLV)-1 engage exosomes for spreading and infection. Exosomes from virus-infected cells transfer viral components such as miRNAs and proteins that promote infection and inflammation. Additionally, these exosomes deliver virus receptors to target cells that make them susceptible to virus entry. HIV-1 infected cells release exosomes that contribute to the pathogenesis including neurological disorders and malignancy. Exosomes can also potentially carry out as a modern approach for the development of HIV-1 and HTLV-1 vaccines. Furthermore, as exosomes are present in most biological fluids, they hold the supreme capacity for clinical usage in the early diagnosis and prognosis of viral infection and associated diseases. Our current knowledge of exosomes' role from virus-infected cells may provide an avenue for efficient retroviruses associated with disease prevention. However, the exact mechanism involved in retroviruses infection/ inflammation remains elusive and related exosomes research will shed light on the mechanisms of pathogenesis.

The Post-transcriptional Regulator Rex of the Human T-Cell Leukemia Virus Type I Is Present as Nucleolar Speckles in Infected Cells

1995 ◽  
Vol 219 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Tetsuya Nosaka ◽  
Yukio Miyazaki ◽  
Tetsurou Takamatsu ◽  
Kouichi Sano ◽  
Masuyo Nakai ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Transcriptional Regulator ◽  
Type I ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells

scholarly journals Robust HIV-1 replication in the absence of integrase function

2020 ◽  
Author(s):  
Ishak D. Irwan ◽  
Heather L. Karnowski ◽  
Hal P. Bogerd ◽  
Kevin Tsai ◽  
Bryan R. Cullen
Keyword(s):  
Transcription Factor ◽  
Leukemia Virus ◽  
Epigenetic Silencing ◽  
Epigenetic Marks ◽  
Proviral Dna ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Circular Dnas ◽  
Episomal Dna ◽  
Hiv 1

AbstractIntegration of the proviral DNA intermediate into the host cell genome represents an essential step in the retroviral life cycle. While the reason(s) for this requirement remains unclear, it is known that unintegrated proviral DNA is epigenetically silenced. Here, we demonstrate that HIV-1 mutants lacking functional integrase can mount a robust, spreading infection in cells expressing the Tax transcription factor encoded by human T-cell leukemia virus 1. In these cells, HIV-1 forms episomal DNA circles, analogous to Hepatitis B virus covalently closed circular DNAs (cccDNAs), that are transcriptionally active and fully capable of supporting viral replication. This rescue correlates with the loss of inhibitory epigenetic marks, and the acquisition of activating marks, on histones bound to unintegrated HIV-1 DNA. Thus retroviral DNA integration may have evolved, at least in part, as a mechanism to avoid the epigenetic silencing of extrachromosomal viral DNA by host innate antiviral factors.SignificanceWhile retroviral DNA is synthesized normally after infection by integrase-deficient viruses, the resultant episomal DNA is then epigenetically silenced. Here, we show that expression of the Tax transcription factor encoded by a second human retrovirus, HTLV-1, prevents the epigenetic silencing of unintegrated HIV-1 DNA and instead induces the addition of activating epigenetic marks, and the recruitment of NF-kB/Rel proteins, to the HIV-1 LTR promoter. Moreover, in the presence of Tax, the HIV-1 DNA circles that form in the absence of integrase function are not only efficiently transcribed but also support a spreading, pathogenic IN- HIV-1 infection. Thus, retroviruses have the potential to replicate without integration, as is indeed seen with HBV.

scholarly journals Repression of Tax Expression Is Associated both with Resistance of Human T-Cell Leukemia Virus Type 1-Infected T Cells to Killing by Tax-Specific Cytotoxic T Lymphocytes and with Impaired Tumorigenicity in a Rat Model

2004 ◽  
Vol 78 (8) ◽  
pp. 3827-3836 ◽  
Author(s):  
Machiko Nomura ◽  
Takashi Ohashi ◽  
Keiko Nishikawa ◽  
Hironori Nishitsuji ◽  
Kiyoshi Kurihara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells

ABSTRACT Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). Although the viral transactivation factor, Tax, has been known to have apparent transforming ability, the exact function of Tax in ATL development is still not clear. To understand the role of Tax in ATL development, we introduced short-interfering RNAs (siRNAs) against Tax in a rat HTLV-1-infected T-cell line. Our results demonstrated that expression of siRNA targeting Tax successfully downregulated Tax expression. Repression of Tax expression was associated with resistance of the HTLV-1-infected T cells to Tax-specific cytotoxic-T-lymphocyte killing. This may be due to the direct effect of decreased Tax expression, because the Tax siRNA did not alter the expression of MHC-I, CD80, or CD86. Furthermore, T cells with Tax downregulation appeared to lose the ability to develop tumors in T-cell-deficient nude rats, in which the parental HTLV-1-infected cells induce ATL-like lymphoproliferative disease. These results indicated the importance of Tax both for activating host immune response against the virus and for maintaining the growth ability of infected cells in vivo. Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL.

scholarly journals Frequent clonal proliferation of human T-cell leukemia virus type 1 (HTLV-1)-infected T cells in HTLV-1-associated myelopathy (HAM-TSP)

Blood ◽  
1992 ◽  
Vol 80 (4) ◽  
pp. 1012-1016 ◽  
Author(s):  
Y Furukawa ◽  
J Fujisawa ◽  
M Osame ◽  
M Toita ◽  
S Sonoda ◽  
...  
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Clonal Expansion ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells

Human T-cell leukemia virus type 1 (HTLV-1) integrates its proviruses into random sites in host chromosomal DNA. Random integration of the proviruses was observed in asymptomatic HTLV-1 carriers and patients with HTLV-1-associated myelopathy (HAM/TSP). However, clonal integration has been reported in patients with adult T-cell leukemia (ATL), including that in the smoldering, chronic, and acute states, indicating clonal expansion of infected cells. In this study, we found that about 20% of HAM/TSP patients and their seropositive family members harbored subpopulation(s) of clonally proliferated cells infected with HTLV-1, although they still maintained randomly infected cells as a major population. These clones were stable during examination periods of 4 months to 3 years. However, these carriers or HAM/TSP patients did not show any significant indication of ATL. This extremely high frequency of clonal expansion of HTLV-1-infected cells indicates that some clones of HTLV-1-infected cells have a tendency to proliferate more efficiently than the other population without malignant transformation.

Serological survey of HIV-1, HIV-2 and human T-cell leukemia virus type 1 for suspected AIDS cases in Ghana

AIDS ◽  
1994 ◽  
Vol 8 (9) ◽  
pp. 1257-1261 ◽  
Author(s):  
Osamu Hishida ◽  
Nana K. Ayisi ◽  
Michael Aidoo ◽  
James Brandful ◽  
William Ampofo ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Serological Survey ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Hiv 1

Redox regulation of T-cell turnover by the p13 protein of human T-cell leukemia virus type 1: distinct effects in primary versus transformed cells

Blood ◽  
2010 ◽  
Vol 116 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Micol Silic-Benussi ◽  
Ilaria Cavallari ◽  
Nicola Vajente ◽  
Silvia Vidali ◽  
Luigi Chieco-Bianchi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Leukemia Virus ◽  
Cell Turnover ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells

AbstractThe present study investigated the function of p13, a mitochondrial protein of human T-cell leukemia virus type 1 (HTLV-1). Although necessary for viral propagation in vivo, the mechanism of function of p13 is incompletely understood. Drawing from studies in isolated mitochondria, we analyzed the effects of p13 on mitochondrial reactive oxygen species (ROS) in transformed and primary T cells. In transformed cells (Jurkat, HeLa), p13 did not affect ROS unless the cells were subjected to glucose deprivation, which led to a p13-dependent increase in ROS and cell death. Using RNA interference we confirmed that expression of p13 also influences glucose starvation-induced cell death in the context of HTLV-1–infected cells. ROS measurements showed an increasing gradient from resting to mitogen-activated primary T cells to transformed T cells (Jurkat). Expression of p13 in primary T cells resulted in their activation, an effect that was abrogated by ROS scavengers. These findings suggest that p13 may have a distinct impact on cell turnover depending on the inherent ROS levels; in the context of the HTLV-1 propagation strategy, p13 could increase the pool of “normal” infected cells while culling cells acquiring a transformed phenotype, thus favoring lifelong persistence of the virus in the host.

scholarly journals Two-Step Nature of Human T-Cell Leukemia Virus Type 1 Replication in Experimentally Infected Squirrel Monkeys (Saimiri sciureus)

2001 ◽  
Vol 75 (2) ◽  
pp. 1083-1089 ◽  
Author(s):  
Franck Mortreux ◽  
Mirdad Kazanji ◽  
Anne-Sophie Gabet ◽  
Benoit de Thoisy ◽  
Eric Wattel
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Squirrel Monkeys ◽  
Saimiri Sciureus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells

ABSTRACT After experimental infection of squirrel monkeys (Saimiri sciureus) with human T-cell leukemia virus type 1 (HTLV-1)-infected cells, the virus is transcribed only transiently in circulating blood, spleen, and lymph nodes. Stable disappearance of viral expression occurs at 2 to 3 weeks after inoculation. This coincides with the development of the anti-HTLV-1 immune response and persistent detection of the provirus in peripheral blood mononuclear cells (PBMCs). In this study, the HTLV-1 replication pattern was analyzed over time in PBMCs and various organs from two HTLV-1-infected squirrel monkeys. Real-time quantitative PCR confirmed that PBMCs and lymphoid organs constitute the major reservoirs for HTLV-1. The PCR amplification of HTLV-1 flanking sequences from PBMCs evidenced a pattern of clonal expansion of infected cells identical to that observed in humans. Dissemination of the virus in body compartments appeared to result from cellular transport of the integrated provirus. The circulating proviral burden increased as a function of time in one animal studied over a period of 4 years. The high proviral loads observed in the last samples resulted from the accumulation of infected cells via the extensive proliferation of a restricted number of persistent clones on a background of polyclonally expanded HTLV-1-positive cells. Therefore, HTLV-1 primary infection in squirrel monkeys is a two-step process involving a transient phase of reverse transcription followed by persistent multiplication of infected cells. This suggests that the choice of the target for blocking HTLV-1 replication might depend on the stage of infection.

Methylation of human T-cell leukemia virus proviral DNA and viral RNA expression in short- and long-term cultures of infected cells

Virology ◽  
1984 ◽  
Vol 135 (1) ◽  
pp. 97-104 ◽  
Author(s):  
Michael F. Clarke ◽  
Cecelia D. Trainor ◽  
Dean L. Mann ◽  
Robert C. Gallo ◽  
Marvin S. Reitz
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Viral Rna ◽  
Rna Expression ◽  
Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Infected Cells ◽  
Short And Long Term
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