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Current Topics in Microbiology and... 2003Infection by all enveloped viruses occurs via the fusion of viral and cellular membranes and delivery of the viral nucleocapsid into the cell cytoplasm, after... (Review)
Review
Infection by all enveloped viruses occurs via the fusion of viral and cellular membranes and delivery of the viral nucleocapsid into the cell cytoplasm, after association of the virus with cognate receptors at the cell surface. This process is mediated by viral fusion proteins anchored in the viral envelope and can be defined based on the requirement for low pH to trigger membrane fusion. In viruses that utilize a pH-dependent entry mechanism, such as influenza virus, viral fusion is triggered by the acidic environment of intracellular organelles after uptake of the virus from the cell surface and trafficking to a low-pH compartment. In contrast, in viruses that utilize a pH-independent entry mechanism, such as most retroviruses, membrane fusion is triggered solely by the interaction of the envelope glycoprotein with cognate receptors, often at the cell surface. However, recent work has indicated that the alpharetrovirus, avian sarcoma and leukosis virus (ASLV), utilizes a novel entry mechanism that combines aspects of both pH-independent and pH-dependent entry. In ASLV infection, the interaction of the envelope glycoprotein (Env) with cognate receptors at the cell surface causes an initial conformational change that primes (activates) Env and renders it sensitive to subsequent low-pH triggering from an intracellular compartment. Thus unlike other pH-dependent viruses, ASLV Env is only sensitive to low-pH triggering following interaction with its cognate receptor. In this manuscript we review current research on ASLV Env-receptor interactions and focus on the specific molecular requirements of both the viral fusion protein and cognate receptors for ASLV entry. In addition, we review data pertaining to the novel two-step entry mechanism of ASLV entry and propose a model by which ASLV Env elicits membrane fusion.
Topics: Alpharetrovirus; Animals; Avian Leukosis Virus; Avian Sarcoma Viruses; Birds; Glycoproteins; Models, Genetic; Receptors, Virus; Viral Envelope Proteins
PubMed: 12932076
DOI: 10.1007/978-3-642-19012-4_3 -
Journal of Virology Dec 2007The mammalian APOBEC3 family of cytidine deaminases includes members that can act as potent inhibitors of retroviral infectivity and retrotransposon mobility. Here, we...
The mammalian APOBEC3 family of cytidine deaminases includes members that can act as potent inhibitors of retroviral infectivity and retrotransposon mobility. Here, we have examined whether the alpharetrovirus Rous sarcoma virus (RSV) is susceptible to inhibition by a range of human APOBEC3 proteins. We report that RSV is highly susceptible to inhibition by human APOBEC3G, APOBEC3F, and APOBEC3B and moderately susceptible to inhibition by human APOBEC3C and APOBEC3A. For all five proteins, inhibition of RSV infectivity was associated with selective virion incorporation and with C-to-T editing of the proviral DNA minus strand. In the case of APOBEC3G, editing appeared to be critical for effective inhibition. These data represent the first report of inhibition of retroviral infectivity and induction of proviral DNA editing by human APOBEC3A and reveal that alpharetroviruses, which do not normally encounter APOBEC3 proteins in their avian hosts, are susceptible to inhibition by all human APOBEC3 proteins tested. These data further suggest that the resistance of mammalian retroviruses to inhibition by the APOBEC3 proteins expressed in their normal host species is likely to have evolved subsequent to the appearance of this family of mammalian antiretroviral proteins some 35 million years ago; i.e., the base state of a naïve retrovirus is susceptibility to inhibition.
Topics: APOBEC Deaminases; APOBEC-3G Deaminase; Animals; Cell Line; Cytidine Deaminase; Cytosine Deaminase; Humans; Minor Histocompatibility Antigens; Proviruses; Quail; RNA Editing; Rous sarcoma virus; Transfection; Virion; Virus Assembly; Virus Replication
PubMed: 17913830
DOI: 10.1128/JVI.01646-07 -
Advances in Experimental Medicine and... 2013The retrovirus family contains several important human and animal pathogens, including the human immunodeficiency virus (HIV), the causative agent of acquired... (Review)
Review
The retrovirus family contains several important human and animal pathogens, including the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Studies with retroviruses were instrumental to our present understanding of the cellular entry of enveloped viruses in general. For instance, studies with alpharetroviruses defined receptor engagement, as opposed to low pH, as a trigger for the envelope protein-driven membrane fusion. The insights into the retroviral entry process allowed the generation of a new class of antivirals, entry inhibitors, and these therapeutics are at present used for treatment of HIV/AIDS. In this chapter, we will summarize key concepts established for entry of avian sarcoma and leukosis virus (ASLV), a widely used model system for retroviral entry. We will then review how foamy virus and HIV, primate- and human retroviruses, enter target cells, and how the interaction of the viral and cellular factors involved in the cellular entry of these viruses impacts viral tropism, pathogenesis and approaches to therapy and vaccine development.
Topics: Animals; Avian Leukosis Virus; Avian Sarcoma Viruses; HIV; Humans; Hydrogen-Ion Concentration; Receptors, Virus; Retroviridae; Viral Tropism; Virus Internalization; env Gene Products, Human Immunodeficiency Virus
PubMed: 23884589
DOI: 10.1007/978-1-4614-7651-1_7 -
Frontiers in Bioscience : a Journal and... May 2008Upon integration into the host chromosome, retroviral gene expression requires transcription by the host RNA polymerase II, and viral messages are subject RNA processing... (Review)
Review
Upon integration into the host chromosome, retroviral gene expression requires transcription by the host RNA polymerase II, and viral messages are subject RNA processing events including 5'-end capping, pre-mRNA splicing, and polyadenylation. At a minimum, RNA splicing is required to generate the env mRNA, but viral replication requires substantial amounts of unspliced RNA to serve as mRNA and for incorporation into progeny virions as genomic RNA. Therefore, splicing has to be controlled to preserve the large unspliced RNA pool. Considering the current view that splicing and polyadenylation are coupled, the question arises as to how genome-length viral RNA is efficiently polyadenylated in the absence of splicing. Polyadenylation of many retroviral mRNAs is inefficient; in avian retroviruses, approximately 15 percent of viral transcripts extend into and are polyadenylated at downstream host genes, which often has profound biological consequences. Retroviruses have served as important models to study RNA processing and this review summarizes a body of work using avian retroviruses that has led to the discovery of novel RNA splicing and polyadenylation control mechanisms.
Topics: Alpharetrovirus; RNA Precursors; RNA Processing, Post-Transcriptional; RNA Splicing; RNA, Messenger; RNA, Viral; Rous sarcoma virus
PubMed: 18508481
DOI: 10.2741/2975 -
Gene Amplification and Analysis 1986The highly conserved, single copy c-myb gene has been independently transduced by two avian acute leukemia viruses, AMV and E26. This gene has also undergone insertional... (Review)
Review
The highly conserved, single copy c-myb gene has been independently transduced by two avian acute leukemia viruses, AMV and E26. This gene has also undergone insertional mutagenesis by non-acutely transforming murine leukemia viruses in a number of hematopoietic tumors. The common denominator of these retroviral activations of c-myb appears to be truncation of the normal coding region at either or both ends. The role of point mutations in myb-induced leukemogenesis is currently unknown. The products of the c-myb gene and its altered viral counterparts are nuclear proteins, a large fraction of which are associated with the nuclear matrix. In addition, the myb gene products have short half-lives and bind DNA in vitro. These features suggest that myb may act by regulating DNA replication or transcription. Consistent with this notion, the expression of c-myb is cell cycle dependent in several cell types. However, the abundant expression of c-myb in the thymus is not similarly regulated and may serve a different function. The expression of c-myb appears not to be limited to hematopoietic tissues as previously thought and the nature of the hematopoietic specificity of transformation by v-myb is not currently understood. Nevertheless, hematopoietic growth factors and their receptors appear to play an important role in such transformation. Two new experimental systems for studying myb have recently been described. First, the discovery of a myb-related gene in Drosophila should allow the application of powerful classical and molecular genetic approaches. The functional similarity of this distantly related gene to the much more closely related avian and mammalian myb genes is unknown. Second, recent studies of murine myb in normal and abnormal hematopoiesis offers several advantages relative to the avian system, such as in-bred animal strains, a wealth of specific cell-surface markers, and cloned hematopoietic growth factor and receptor genes. Isolation or construction of an acutely transforming murine myb retrovirus may thus be very useful. Several obvious goals for future research will be to define the function of myb proteins within the nucleus, to understand the regulation of myb expression during the cell cycle, to establish which molecular alterations are essential for converting c-myb into a transforming gene, and the determine the role of myb in human malignancies.
Topics: Alpharetrovirus; Avian Myeloblastosis Virus; Cell Transformation, Viral; Gene Expression Regulation; Genes, Viral; Oncogene Proteins v-myb; Oncogenes; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-myb; Proto-Oncogenes; Retroviridae Proteins; Transcription, Genetic
PubMed: 3333362
DOI: No ID Found -
Viruses Dec 2014Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However,... (Review)
Review
Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However, vector-mediated adverse events related to insertional mutagenesis were also observed, emphasizing the need for safer therapeutic vectors. Paradoxically, alpharetroviruses, originally discovered as cancer-causing agents, have a more random and potentially safer integration pattern compared to gammaretro- and lentiviruses. In this review, we provide a short overview of the history of alpharetroviruses and explain how they can be converted into state-of-the-art gene delivery tools with improved safety features. We discuss development of alpharetroviral vectors in compliance with regulatory requirements for clinical translation, and provide an outlook on possible future gene therapy applications. Taken together, this review is a broad overview of alpharetroviral vectors spanning the bridge from their parental virus discovery to their potential applicability in clinical settings.
Topics: Alpharetrovirus; Animals; Genetic Therapy; Genetic Vectors; Humans; Neoplasms; Virus Integration
PubMed: 25490763
DOI: 10.3390/v6124811 -
The Journal of General Virology Jan 1979
Review
Topics: Alpharetrovirus; Base Sequence; DNA, Viral; Genes; Genes, Viral; Leukemia Virus, Murine; Nucleic Acid Conformation; RNA, Messenger; RNA, Viral; Recombination, Genetic
PubMed: 215703
DOI: 10.1099/0022-1317-42-1-1 -
Current Topics in Microbiology and... 1978
Review
Topics: Alpharetrovirus; Animals; Antibodies, Viral; Antigens, Viral; Avian Leukosis; Avian Leukosis Virus; Chickens; Genes; Genes, Viral; Glycoproteins; Protein Biosynthesis; Recombination, Genetic; Transcription, Genetic; Viral Proteins
PubMed: 215385
DOI: 10.1007/978-3-642-67087-9_1 -
Current Topics in Microbiology and... 1983
Review
Topics: Alpharetrovirus; Animals; Avian Leukosis Virus; Avian Myeloblastosis Virus; Birds; Cell Differentiation; Cell Transformation, Neoplastic; Cell Transformation, Viral; Erythroblasts; Fibroblasts; Gene Expression Regulation; Genes, Viral; Granulocytes; Macrophages; Mammals; Oncogenes; Viral Proteins
PubMed: 6303707
DOI: 10.1007/978-3-642-68943-7_5 -
Oncogene Dec 2000Studies of retroviral-induced oncogenesis in animal systems led to the initial discovery of viral oncogenes and their cellular homologs, and provided critical insights... (Review)
Review
Studies of retroviral-induced oncogenesis in animal systems led to the initial discovery of viral oncogenes and their cellular homologs, and provided critical insights into their role in the neoplastic process. V-ets, the founding member of the ETS oncogene family, was originally identified as part of the fusion oncogene encoded by the avian acute leukemia virus E26 and subsequent analysis of virus induced leukemias led to the initial isolation of two other members of the ETS gene family. PU.1 was identified as a target of insertional activation in the majority of tumors induced by the murine Spleen Focus Forming virus (SFFV), while fli-1 proved to be the target of Friend murine leukemia virus (F-MuLV) in F-MuLV induced erythroleukemia, as well as that of the 10A1 and Graffi viruses. The common features of the erythroid and myeloid diseases induced by these viruses provided the initial demonstration that these and other members of the ETS family play important roles in hematopoietic development as well as disease. This review provides an overview of the role of ETS genes in retrovirally induced neoplasia, their possible mechanisms of action, and how these viral studies relate to current knowledge of the functions of these genes in hematopoiesis.
Topics: 3T3 Cells; Alpharetrovirus; Animals; Avian Myeloblastosis Virus; Cell Transformation, Viral; Chickens; DNA-Binding Proteins; Fibroblasts; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Hematopoiesis; Humans; Leukemia Virus, Murine; Mice; Multigene Family; Mutagenesis, Insertional; Oncogenes; Proto-Oncogene Protein c-fli-1; Proto-Oncogene Proteins; Proviruses; Retroviridae; Spleen Focus-Forming Viruses; Trans-Activators
PubMed: 11175363
DOI: 10.1038/sj.onc.1204046