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Critical Reviews in Microbiology Nov 2018The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these... (Review)
Review
The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these are defective or silenced through epigenetic changes, they were historically considered "junk DNA" and their potential role in human physiology or pathological circumstances have been poorly studied. The most recently acquired, human endogenous retrovirus-K (HERV-K), has multiple copies in the human genome and some of them have complete open reading frames that are transcribed and translated, especially in early embryogenesis. Phylogenetically, HERV-K is considered a supergroup of viruses. One of the subtypes, termed HML-2, seems to be the most active and hence, it is the best studied. Aberrant expression of HML-2 in adult tissues has been associated with certain types of cancer and with neurodegenerative diseases. This review discusses the discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis. Finally, it presents different therapeutic approaches being considered to target these viruses.
Topics: Animals; Endogenous Retroviruses; Genome, Human; Humans; Retroviridae; Retroviridae Infections; Virus Replication
PubMed: 30318978
DOI: 10.1080/1040841X.2018.1501345 -
Viruses May 2022This review is an accompaniment to a Special Issue on "Retroviral RNA Processing". It discusses post-transcriptional regulation of retroviruses, ranging from the ancient... (Review)
Review
This review is an accompaniment to a Special Issue on "Retroviral RNA Processing". It discusses post-transcriptional regulation of retroviruses, ranging from the ancient foamy viruses to more modern viruses, such as HIV-1, HTLV-1, Rous sarcoma virus, murine leukemia virus, mouse mammary tumor virus, and Mason-Pfizer monkey virus. This review is not comprehensive. However, it tries to address some of the major questions in the field with examples of how different retroviruses express their genes. It is amazing that a single primary RNA transcript can have so many possible fates: genomic RNA, unspliced mRNA, and up to 50 different alternatively spliced mRNAs. This review will discuss the sorting of RNAs for packaging or translation, RNA nuclear export mechanisms, splicing, translation, RNA modifications, and avoidance of nonsense-mediated RNA decay.
Topics: Active Transport, Cell Nucleus; Animals; Leukemia Virus, Murine; Mice; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Viral; Retroviridae
PubMed: 35632854
DOI: 10.3390/v14051113 -
Viruses Jan 2022Stephen Oroszlan received his early education in Hungary, graduating in 1950 from the Technical University in Budapest with a degree in chemical engineering [...].
Stephen Oroszlan received his early education in Hungary, graduating in 1950 from the Technical University in Budapest with a degree in chemical engineering [...].
Topics: History, 20th Century; History, 21st Century; Humans; Male; Retroviridae; Retroviridae Proteins; Viral Protease Inhibitors; Viral Proteases
PubMed: 35215882
DOI: 10.3390/v14020290 -
Current Opinion in Virology Jun 2019During retrovirus maturation, cleavage of the precursor structural Gag polyprotein by the viral protease induces architectural rearrangement of the virus particle from... (Review)
Review
During retrovirus maturation, cleavage of the precursor structural Gag polyprotein by the viral protease induces architectural rearrangement of the virus particle from an immature into a mature, infectious form. The structural rearrangement encapsidates the viral RNA genome in a fullerene capsid, producing a diffusible viral core that can initiate infection upon entry into the cytoplasm of a host cell. Maturation is an important therapeutic window against HIV-1. In this review, we highlight recent breakthroughs in understanding of the structures of retroviral immature and mature capsid lattices that define the boundary conditions of maturation and provide novel insights on capsid transformation. We also discuss emerging insights on encapsidation of the viral genome in the mature capsid, as well as remaining questions for further study.
Topics: Capsid; Capsid Proteins; Genome, Viral; HIV-1; Models, Molecular; Peptide Hydrolases; RNA, Viral; Retroviridae; Virion; Virus Assembly
PubMed: 31185449
DOI: 10.1016/j.coviro.2019.05.004 -
Viruses May 2022Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles.... (Review)
Review
Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles. Retroviral RNA packaging requires RNA export of the unspliced genomic RNA from the nucleus, translocation of the genome to virus assembly sites, and specific interaction with Gag, the main viral structural protein. While some aspects of the RNA packaging process are understood, many others remain poorly understood. In this review, we provide an update on recent advancements in understanding the mechanism of RNA packaging for retroviruses that cause disease in humans, i.e., HIV-1, HIV-2, and HTLV-1, as well as advances in the understanding of the details of genomic RNA nuclear export, genome translocation to virus assembly sites, and genomic RNA dimerization.
Topics: Genomics; HIV-1; Humans; RNA, Viral; Retroviridae; Virus Assembly
PubMed: 35632835
DOI: 10.3390/v14051094 -
Clinical Microbiology and Infection :... Apr 2016Retroviruses, including the human immunodeficiency virus (HIV), are notorious for two essential steps of their viral replication: reverse transcription and integration.... (Review)
Review
Retroviruses, including the human immunodeficiency virus (HIV), are notorious for two essential steps of their viral replication: reverse transcription and integration. This latter property is considered to be essential for productive replication and ensures the stable long-term insertion of the viral genome sequence in the host chromatin, thereby leading to the life-long association of the virus with the infected cell. Using HIV as a prototypic example, the present review aims to provide an overview of how and where integration occurs, as well as presenting general consequences for both the virus and the infected host.
Topics: Host-Pathogen Interactions; Humans; Retroviridae; Virus Integration
PubMed: 27107301
DOI: 10.1016/j.cmi.2016.02.013 -
Retrovirology Feb 2018Retroviruses can cause severe diseases such as cancer and acquired immunodeficiency syndrome. A unique feature in the life cycle of retroviruses is that their RNA genome... (Review)
Review
Retroviruses can cause severe diseases such as cancer and acquired immunodeficiency syndrome. A unique feature in the life cycle of retroviruses is that their RNA genome is reverse transcribed into double-stranded DNA, which then integrates into the host genome to exploit the host machinery for their benefits. The metazoan genome encodes numerous non-coding RNAs (ncRNA), which act as key regulators in essential cellular processes such as antiviral response. The development of next-generation sequencing technology has greatly accelerated the detection of ncRNAs from viruses and their hosts. ncRNAs have been shown to play important roles in the retroviral life cycle and virus-host interactions. Here, we review recent advances in ncRNA studies with special focus on those have changed our understanding of retroviruses or provided novel strategies to treat retrovirus-related diseases. Many ncRNAs such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are involved in the late phase of the retroviral life cycle. However, their roles in the early phase of viral replication merit further investigations.
Topics: Gene Expression Regulation, Viral; Host-Pathogen Interactions; Humans; MicroRNAs; RNA Interference; RNA, Long Noncoding; RNA, Untranslated; Retroviridae; Retroviridae Infections; Virus Latency
PubMed: 29426337
DOI: 10.1186/s12977-018-0403-8 -
Viruses Nov 2021Retroviral infection delivers an RNA genome into the cytoplasm that serves as the template for the synthesis of a linear double-stranded DNA copy by the viral reverse... (Review)
Review
Retroviral infection delivers an RNA genome into the cytoplasm that serves as the template for the synthesis of a linear double-stranded DNA copy by the viral reverse transcriptase. Within the nucleus this linear DNA gives rise to extrachromosomal circular forms, and in a key step of the life cycle is inserted into the host genome to form the integrated provirus. The unintegrated DNA forms, like those of DNAs entering cells by other means, are rapidly loaded with nucleosomes and heavily silenced by epigenetic histone modifications. This review summarizes our present understanding of the silencing machinery for the DNAs of the mouse leukemia viruses and human immunodeficiency virus type 1. We consider the potential impact of the silencing on virus replication, on the sensing of the virus by the innate immune system, and on the formation of latent proviruses. We also speculate on the changeover to high expression from the integrated proviruses in permissive cell types, and briefly consider the silencing of proviruses even after integration in embryonic stem cells and other developmentally primitive cell types.
Topics: Animals; DNA, Viral; Gene Silencing; HIV-1; Histone Code; Humans; Leukemia Virus, Murine; Proviruses; Retroviridae; Transcription, Genetic; Virus Integration; Virus Replication
PubMed: 34835055
DOI: 10.3390/v13112248 -
Viruses Sep 2019Foamy viruses (FVs), also known as spumaretroviruses, are complex retroviruses that are seemingly nonpathogenic in natural hosts. In natural hosts, which include... (Review)
Review
Foamy viruses (FVs), also known as spumaretroviruses, are complex retroviruses that are seemingly nonpathogenic in natural hosts. In natural hosts, which include felines, bovines, and nonhuman primates (NHPs), a large percentage of adults are infected with FVs. For this reason, the effect of FVs on infections with other viruses (co-infections) cannot be easily studied in natural populations. Most of what is known about interactions between FVs and other viruses is based on studies of NHPs in artificial settings such as research facilities. In these settings, there is some indication that FVs can exacerbate infections with lentiviruses such as simian immunodeficiency virus (SIV). Nonhuman primate (NHP) simian FVs (SFVs) have been shown to infect people without any apparent pathogenicity. Humans zoonotically infected with simian foamy virus (SFV) are often co-infected with other viruses. Thus, it is important to know whether SFV co-infections affect human disease.
Topics: Animals; Cats; Coinfection; Humans; Retroviridae; Retroviridae Infections; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Simian foamy virus; Spumavirus; Zoonoses
PubMed: 31569704
DOI: 10.3390/v11100902 -
Viruses Dec 2021Retroviruses have a very complex and tightly controlled life cycle which has been studied intensely for decades. After a virus enters the cell, it reverse-transcribes... (Review)
Review
Retroviruses have a very complex and tightly controlled life cycle which has been studied intensely for decades. After a virus enters the cell, it reverse-transcribes its genome, which is then integrated into the host genome, and subsequently all structural and regulatory proteins are transcribed and translated. The proteins, along with the viral genome, assemble into a new virion, which buds off the host cell and matures into a newly infectious virion. If any one of these steps are faulty, the virus cannot produce infectious viral progeny. Recent advances in structural and molecular techniques have made it possible to better understand this class of viruses, including details about how they regulate and coordinate the different steps of the virus life cycle. In this review we summarize the molecular analysis of the assembly and maturation steps of the life cycle by providing an overview on structural and biochemical studies to understand these processes. We also outline the differences between various retrovirus families with regards to these processes.
Topics: Capsid; Cryoelectron Microscopy; Genome, Viral; HIV-1; Humans; Models, Molecular; Retroviridae; Virion; Virus Assembly
PubMed: 35062258
DOI: 10.3390/v14010054