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Viruses Sep 2020Recent commercialization of lentiviral vector (LV)-based cell therapies and successful reports of clinical studies have demonstrated the untapped potential of LVs to... (Review)
Review
Recent commercialization of lentiviral vector (LV)-based cell therapies and successful reports of clinical studies have demonstrated the untapped potential of LVs to treat diseases and benefit patients. LVs hold notable and inherent advantages over other gene transfer agents based on their ability to transduce non-dividing cells, permanently transform target cell genome, and allow stable, long-term transgene expression. LV systems based on non-human lentiviruses are attractive alternatives to conventional HIV-1-based LVs due to their lack of pathogenicity in humans. This article reviews non-human lentiviruses and highlights their unique characteristics regarding virology and molecular biology. The LV systems developed based on these lentiviruses, as well as their successes and shortcomings, are also discussed. As the field of gene therapy is advancing rapidly, the use of LVs uncovers further challenges and possibilities. Advances in virology and an improved understanding of lentiviral biology will aid in the creation of recombinant viral vector variants suitable for translational applications from a variety of lentiviruses.
Topics: Animals; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; HIV-1; Humans; Lentivirus; Lentiviruses, Feline; Retroviridae; Transgenes
PubMed: 33003635
DOI: 10.3390/v12101106 -
Archives of Virology Apr 2021Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and they produce viral particles that are able to infect human cells and therefore pose... (Review)
Review
Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and they produce viral particles that are able to infect human cells and therefore pose a special risk for xenotransplantation. In contrast to other pig microorganisms that also pose a risk, such as porcine cytomegalovirus and hepatitis E virus, PERVs cannot be eliminated from pigs by vaccines, antiviral drugs, early weaning, or embryo transfer. Since PERVs are relevant for xenotransplantation, their biology and origin are of great interest. Recent studies have shown that PERVs are the result of a transspecies transmission of precursor retroviruses from different animals and further evolution in the pig genome. PERVs acquired different long terminal repeats (LTRs), and recombination took place. In parallel, it has been shown that the activity of the LTRs and recombination in the envelope are important for the transmissibility and pathogenesis of PERVs. Transspecies transmission of retroviruses is common, a well-known example being the transmission of precursor retroviruses from non-human primates to humans, resulting in human immunodeficiency virus (HIV). Here, recent findings concerning the origin of PERVs, their LTRs, and recombination events that occurred during evolution are reviewed and compared with other findings regarding transspecies transmission of retroviruses.
Topics: Animals; Endogenous Retroviruses; Evolution, Molecular; Genome, Viral; Humans; Prevalence; Recombination, Genetic; Retroviridae; Swine; Zoonoses
PubMed: 33547957
DOI: 10.1007/s00705-020-04925-8 -
Virologica Sinica Aug 2023Equine infectious anemia virus (EIAV) is a member of the lentivirus genus in the Retroviridae family and is considered an animal model for HIV/AIDS research. An... (Review)
Review
Equine infectious anemia virus (EIAV) is a member of the lentivirus genus in the Retroviridae family and is considered an animal model for HIV/AIDS research. An attenuated EIAV vaccine, which was successfully developed in the 1970s by classical serial passage techniques, is the first and only lentivirus vaccine that has been widely used to date. Restriction factors are cellular proteins that provide an early line of defense against viral replication and spread by interfering with various critical steps in the viral replication cycle. However, viruses have evolved specific mechanisms to overcome these host barriers through adaptation. The battle between the viruses and restriction factors is actually a natural part of the viral replication process, which has been well studied in human immunodeficiency virus type 1 (HIV-1). EIAV has the simplest genome composition of all lentiviruses, making it an intriguing subject for understanding how the virus employs its limited viral proteins to overcome restriction factors. In this review, we summarize the current literature on the interactions between equine restriction factors and EIAV. The features of equine restriction factors and the mechanisms by which the EIAV counteract the restriction suggest that lentiviruses employ diverse strategies to counteract innate immune restrictions. In addition, we present our insights on whether restriction factors induce alterations in the phenotype of the attenuated EIAV vaccine.
Topics: Horses; Animals; Humans; Infectious Anemia Virus, Equine; Antiviral Restriction Factors; Viral Proteins; Virus Replication; HIV-1
PubMed: 37419416
DOI: 10.1016/j.virs.2023.07.001 -
Retrovirology May 2023Most proteins expressed by endogenous and exogenous retroviruses are encoded in the sense (positive) strand of the genome and are under the control of regulatory... (Review)
Review
Most proteins expressed by endogenous and exogenous retroviruses are encoded in the sense (positive) strand of the genome and are under the control of regulatory elements within the 5' long terminal repeat (LTR). A number of retroviral genomes also encode genes in the antisense (negative) strand and their expression is under the control of negative sense promoters within the 3' LTR. In the case of the Human T-cell Lymphotropic Virus 1 (HTLV-1), the antisense protein HBZ has been shown to play a critical role in the virus lifecycle and in the pathogenic process, while the function of the Human Immunodeficiency Virus 1 (HIV-1) antisense protein ASP remains unknown. However, the expression of 3' LTR-driven antisense transcripts is not always demonstrably associated with the presence of an antisense open reading frame encoding a viral protein. Moreover, even in the case of retroviruses that do express an antisense protein, such as HTLV-1 and the pandemic strains of HIV-1, the 3' LTR-driven antisense transcript shows both protein-coding and noncoding activities. Indeed, the ability to express antisense transcripts appears to be phylogenetically more widespread among endogenous and exogenous retroviruses than the presence of a functional antisense open reading frame within these transcripts. This suggests that retroviral antisense transcripts may have originated as noncoding molecules with regulatory activity that in some cases later acquired protein-coding function. Here, we will review examples of endogenous and exogenous retroviral antisense transcripts, and the ways through which they benefit viral persistence in the host.
Topics: Humans; Human T-lymphotropic virus 1; Deltaretrovirus; Viral Proteins; Promoter Regions, Genetic; HIV-1
PubMed: 37194028
DOI: 10.1186/s12977-023-00622-x -
Journal of Feline Medicine and Surgery Mar 2022
Topics: Animals; Cats; Immunodeficiency Virus, Feline; Leukemia Virus, Feline; Reproduction
PubMed: 35209769
DOI: 10.1177/1098612X221079705 -
Virologie (Montrouge, France) Dec 2020In this review, we summarize recent advances in the knowledge of the biological functions of human TRIM5α, a cytoplasmic protein mostly known for its antiretroviral... (Review)
Review
In this review, we summarize recent advances in the knowledge of the biological functions of human TRIM5α, a cytoplasmic protein mostly known for its antiretroviral functions. In addition to directly targeting retroviral capsid cores, an inhibitory activity called "restriction", TRIM5α senses retroviruses and activates NF-κB and AP-1 signaling pathways, resulting in the production of type I interferon (IFN-I). The antiviral state resulting from the activation of these pathways includes the upregulation of other restriction factors, and is thought to be important for the control of HIV-1 in some patients. TRIM5α also targets the protease enzyme of several tick-borne flaviviruses, a family of viruses not closely related to retroviruses. In addition to these antiviral functions, TRIM5α promotes autophagy by interacting with key actors of this pathway, such as ULK1 and p62. TRIM5α may function as a selective autophagy receptor in some conditions. Altogether, our understanding of TRIM5α shows its potential for the development of medical applications in viral diseases and beyond.
Topics: Antiviral Agents; Antiviral Restriction Factors; Capsid; Carrier Proteins; HIV-1; Humans; Retroviridae; Tripartite Motif Proteins; Ubiquitin-Protein Ligases
PubMed: 33441289
DOI: 10.1684/vir.2020.0869 -
American Journal of Reproductive... Feb 2021Cells produce cytoplasmic vesicles to facilitate the processing and transport of RNAs, proteins, and other signaling molecules among intracellular organelles. Moreover,... (Review)
Review
Cells produce cytoplasmic vesicles to facilitate the processing and transport of RNAs, proteins, and other signaling molecules among intracellular organelles. Moreover, most cells release a range of extracellular vesicles (EVs) that mediate intercellular communication in both physiological and pathological settings. In addition to a better understanding of their biological functions, the diagnostic and therapeutic prospects of EVs, particularly the nano-sized small EVs (sEVs, exosomes), are currently being rigorously pursued. While EVs and viruses such as retroviruses might have evolved independently, they share a number of similar characteristics, including biogenesis pathways, size distribution, cargo, and cell-targeting mechanisms. The interplay of EVs with viruses has profound effects on viral replication and infectivity. Our research indicates that sEVs, produced by primary human trophoblasts, can endow other non-placental cell types with antiviral response. Better insights into the interaction of EVs with viruses may illuminate new ways to attenuate viral infections during pregnancy, and perhaps develop new antiviral therapeutics to protect the feto-placental unit during critical times of human development.
Topics: Extracellular Vesicles; Female; Humans; Nanostructures; Organ Specificity; Placenta; Pregnancy; Retroviridae; Retroviridae Infections; Trophoblasts; Virulence; Virus Replication
PubMed: 32939907
DOI: 10.1111/aji.13345 -
Frontiers in Immunology 2022Exogenous retroviruses such as human immunodeficiency virus type 1 (HIV-1), human T-cell leukemia virus type 1 (HTLV-1) and bovine leukemia virus (BLV) can cause various... (Review)
Review
Exogenous retroviruses such as human immunodeficiency virus type 1 (HIV-1), human T-cell leukemia virus type 1 (HTLV-1) and bovine leukemia virus (BLV) can cause various diseases including immunodeficiency, inflammatory diseases and hematologic malignancies. These retroviruses persistently infect their hosts. Therefore, they need to evade host immune surveillance. One way in which these viruses might avoid immune detection is to utilize functional RNAs, rather than proteins, for certain activities, because RNAs are not recognized by the host immune system. HTLV-1 encodes the () gene in the antisense strand of the provirus. The HBZ protein is constantly expressed in HTLV-1 carriers and patients with adult T-cell leukemia-lymphoma, and it plays critical roles in pathogenesis. However, not only encodes this protein, but also functions as mRNA. Thus, gene mRNA is bifunctional. HIV-1 and BLV also encode long non-coding RNAs as antisense transcripts. In this review, we reshape our current understanding of how these antisense transcripts function and how they influence disease pathogenesis.
Topics: Basic-Leucine Zipper Transcription Factors; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; RNA, Messenger; Retroviridae Proteins
PubMed: 35572593
DOI: 10.3389/fimmu.2022.875211 -
Xenotransplantation Nov 2019
Review
Topics: Animals; Endogenous Retroviruses; Heterografts; Humans; Publications; Research; Retroviridae Infections; Transplantation, Heterologous
PubMed: 31762126
DOI: 10.1111/xen.12573 -
Current Protocols Oct 2022Inflammasomes are multiprotein complexes that play key roles in the host's innate immune response to insult. The assembly of an inflammatory complex is initiated with...
Inflammasomes are multiprotein complexes that play key roles in the host's innate immune response to insult. The assembly of an inflammatory complex is initiated with the oligomerization of the upstream inflammasome-forming sensor and then follows a well-orchestrated multi-step process leading to downstream effector functions that are critical in the innate immune response. The final assembly of these steps provides a detectable readout of inflammasome complex activation in the form of an apoptosis-associated speck-like protein containing a CARD (ASC) speck. Inflammasome activation-and the release of IL-1β and ASC specks from the microglia, the brain resident immune cell-have been implicated in various neurological and neurodegenerative disorders. Protocols exist for the generation of fluorescent inflammasome indicator peripheral macrophages. Building upon these protocols, we describe here a protocol that details the generation of fluorescent inflammasome indicator microglia cells using recombinant retroviruses to transduce murine BV-2 cells. In this protocol, the cells are established in a manner to allow for experimental control of the initial priming step of the inflammasome activation process. We then provide a series of steps for using these reporter cells within an inflammasome activation assay and use real-time imaging of ASC-speck formation as an indicator of inflammasome activation. In addition, we describe strategies for using these cells for examining the effects of a test substance on inflammasome activation. This protocol offers an effective approach conducive to screening for and examining modifications of microglia inflammasome activation due to exposure to chemicals or pharmacological agents. © Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Production of retroviruses to express inflammasome indicator Basic Protocol 2: Generation of inflammasome indicator BV-2 cells Basic Protocol 3: Priming and activation of BV-2-ASC-Cerulean cells for inflammasome activation assay Basic Protocol 4: Examining modifications to inflammasome activation by test substances Basic Protocol 5: Imaging and analysis of ASC speck formation.
Topics: Mice; Animals; Inflammasomes; CARD Signaling Adaptor Proteins; Microglia; Macrophages; Immunity, Innate; Retroviridae
PubMed: 36286528
DOI: 10.1002/cpz1.578