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Voprosy Virusologii Dec 2023The review article conducts an in-depth analysis of information gleaned from a comprehensive literature search across Scopus, Web of Science, and MedLine databases. The... (Review)
Review
The review article conducts an in-depth analysis of information gleaned from a comprehensive literature search across Scopus, Web of Science, and MedLine databases. The focal point of this search revolves around the identification and exploration of the mechanisms orchestrated by host cell factors in the replication cycle of the human immunodeficiency virus (HIV-1, Retroviridae: ). The article delves into two primary categories of proteins, namely HIV dependence factors (such as CypA, LEDGF, TSG101) and restriction factors (including SERINС5, TRIM5α, APOBEC3G), providing illustrative examples. The current understanding of the functioning mechanisms of these proteins is elucidated, and an evaluation is presented on the potential development of drugs for treating HIV infection. These drugs aim to either inhibit or stimulate the activity of host factors, offering insights into promising avenues for future research and therapeutic advancements.
Topics: Humans; HIV Infections; Ubiquitin-Protein Ligases; Cell Line; HIV-1; Virus Replication
PubMed: 38156565
DOI: 10.36233/0507-4088-207 -
Viruses Jan 2021The APOBEC3 family of proteins in mammals consists of cellular cytosine deaminases and well-known restriction factors against retroviruses, including lentiviruses.... (Review)
Review
The APOBEC3 family of proteins in mammals consists of cellular cytosine deaminases and well-known restriction factors against retroviruses, including lentiviruses. genes are highly amplified and diversified in mammals, suggesting that their evolution and diversification have been driven by conflicts with ancient viruses. At present, lentiviruses, including HIV, the causative agent of AIDS, are known to encode a viral protein called Vif to overcome the antiviral effects of the APOBEC3 proteins of their hosts. Recent studies have revealed that the acquisition of an anti-APOBEC3 ability by lentiviruses is a key step in achieving successful cross-species transmission. Here, we summarize the current knowledge of the interplay between mammalian APOBEC3 proteins and viral infections and introduce a scenario of the coevolution of mammalian genes and viruses.
Topics: APOBEC Deaminases; Animals; Disease Resistance; Evolution, Molecular; Genetic Variation; Genome, Viral; Host-Pathogen Interactions; Humans; Lentivirus; Phylogeny; Retroviridae; Retroviridae Infections; Species Specificity; vif Gene Products, Human Immunodeficiency Virus
PubMed: 33477360
DOI: 10.3390/v13010124 -
MBio Oct 2023Studying the co-evolution between viruses and humans is important for understanding why we are what we are now as well as for developing future antiviral drugs. Here we...
Studying the co-evolution between viruses and humans is important for understanding why we are what we are now as well as for developing future antiviral drugs. Here we pinned down an evolutionary arms race between retroviruses and mammalian hosts at the molecular level by identifying the antagonism between a host antiviral restriction factor PSGL-1 and viral accessory proteins. We show that this antagonism is conserved from mouse to human and from mouse retrovirus to HIV. Further studying this antagonism might provide opportunities for developing new antiviral therapies.
Topics: Humans; Mice; Animals; Viral Regulatory and Accessory Proteins; Retroviridae; Mammals; Antiviral Agents
PubMed: 37787515
DOI: 10.1128/mbio.00387-23 -
Nature Cell Biology Jan 2022
Topics: Endogenous Retroviruses
PubMed: 34961795
DOI: 10.1038/s41556-021-00758-y -
International Journal of Molecular... Sep 2022Endogenous retroviruses (ERVs), deriving from exogenous retroviral infections of germ line cells occurred millions of years ago, represent ~8% of human genome. Most ERVs... (Review)
Review
Endogenous retroviruses (ERVs), deriving from exogenous retroviral infections of germ line cells occurred millions of years ago, represent ~8% of human genome. Most ERVs are highly inactivated because of the accumulation of mutations, insertions, deletions, and/or truncations. However, it is becoming increasingly apparent that ERVs influence host biology through genetic and epigenetic mechanisms under particular physiological and pathological conditions, which provide both beneficial and deleterious effects for the host. For instance, certain ERVs expression is essential for human embryonic development. Whereas abnormal activation of ERVs was found to be involved in numbers of human diseases, such as cancer and neurodegenerative diseases. Therefore, understanding the mechanisms of regulation of ERVs would provide insights into the role of ERVs in health and diseases. Here, we provide an overview of mechanisms of transcriptional regulation of ERVs and their dysregulation in human diseases.
Topics: Endogenous Retroviruses; Epigenesis, Genetic; Genome, Human; Humans; Retroviridae Infections
PubMed: 36077510
DOI: 10.3390/ijms231710112 -
Viruses Nov 2019Cells that are latently infected with HIV-1 preclude an HIV-1 cure, as antiretroviral therapy does not target this latent population. HIV-1 is highly genetically... (Review)
Review
Cells that are latently infected with HIV-1 preclude an HIV-1 cure, as antiretroviral therapy does not target this latent population. HIV-1 is highly genetically diverse, with over 10 subtypes and numerous recombinant forms circulating worldwide. In spite of this vast diversity, much of our understanding of latency and latency reversal is largely based on subtype B viruses. As such, most of the development of cure strategies targeting HIV-1 are solely based on subtype B. It is currently assumed that subtype does not influence the establishment or reactivation of latent viruses. However, this has not been conclusively proven one way or the other. A better understanding of the factors that influence HIV-1 latency in all viral subtypes will help develop therapeutic strategies that can be applied worldwide. Here, we review the latest literature on subtype-specific factors that affect viral replication, pathogenesis, and, most importantly, latency and its reversal.
Topics: Genetic Variation; Geography; HIV Infections; HIV-1; Humans; Terminal Repeat Sequences; Viral Proteins; Virus Latency; Virus Replication
PubMed: 31795223
DOI: 10.3390/v11121104 -
Cold Spring Harbor Perspectives in... May 2020To date, more than 200 monogenic, often devastating, skin diseases have been described. Because of unmet medical needs, development of long-lasting and curative... (Review)
Review
To date, more than 200 monogenic, often devastating, skin diseases have been described. Because of unmet medical needs, development of long-lasting and curative therapies has been consistently attempted, with the aim of correcting the underlying molecular defect. In this review, we will specifically address the few combined cell and gene therapy strategies that made it to the clinics. Based on these studies, what can be envisioned for the future is a patient-oriented strategy, built on the specific features of the individual in need. Most likely, a combination of different strategies, approaches, and advanced therapies will be required to reach the finish line at the end of the long and winding road hampering the achievement of definitive treatments for genodermatoses.
Topics: Animals; CRISPR-Cas Systems; Epidermis; Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica; Epidermolysis Bullosa, Junctional; Genes, Dominant; Genes, Recessive; Genetic Therapy; Genetic Vectors; Humans; Lentivirus; Netherton Syndrome; Retroviridae; Simplexvirus; Skin; Skin Diseases; Stem Cells
PubMed: 31653644
DOI: 10.1101/cshperspect.a035667 -
Infection, Genetics and Evolution :... Sep 2019Members of the virus families Retroviridae and Hepadnaviridae use reverse transcriptase (RT) to synthesize a DNA copy of their genomic and pregenomic RNA, respectively,... (Review)
Review
Members of the virus families Retroviridae and Hepadnaviridae use reverse transcriptase (RT) to synthesize a DNA copy of their genomic and pregenomic RNA, respectively, during the viral life cycle. A group of viruses belonging to Retroviridae ("acute transforming" retroviruses) as well as human hepatitis B virus (HBV), the prototype member of Hepadnaviridae (hepadnaviruses) are able to cause malignant neoplasms in infected hosts, due to the expression of pleiotropic "transforming proteins" encoded by the genomes of these reverse-transcribing tumor viruses. In this review we wish to compare the common and unique features of replication strategies characteristic of acute transforming retroviruses and HBV and summarize data related to the origin and evolution of their viral oncogenes either via transduction of cellular genes, or by accumulation of mutations in viral sequences that create a new open reading frame (overprinting). The exons of cellular genes (proto-onc genes or c-onc genes) incorporated into the genome of acute transforming retroviruses are regularly affected by deletions resulting in the expression of truncated viral oncoproteins which are frequently dysregulated compared to their cellular counterparts. These retroviral transforming proteins alter the behavior of their target cells (malignant transformation). HBx, a pleiotropic protein of HBV, regulates virus replication and contributes to hepatocarcinogenesis. In contrast to the v-onc genes of acute transforming retroviruses, the viral gene encoding the full-length, wild-type HBx (wtHBx) protein does not have a cellular counterpart. Mutations and deletions frequently affect, however, the HBV genome as well, resulting in the expression of truncated HBx proteins (trHBx) in liver cells. Truncated, especially C-terminal truncated variants of HBx (Ct-HBX proteins), may facilitate initiation and progression of liver carcinoma.
Topics: Animals; Hepatitis B virus; Humans; Liver Neoplasms; Oncogene Proteins; Retroviridae; Virus Replication
PubMed: 31152910
DOI: 10.1016/j.meegid.2019.05.020 -
Retrovirology Sep 2019Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans-as the etiological... (Review)
Review
Of the members of the primate T cell lymphotropic virus (PTLV) family, only the human T-cell leukemia virus type-1 (HTLV-1) causes disease in humans-as the etiological agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other auto-inflammatory disorders. Despite having significant genomic organizational and structural similarities, the closely related human T-cell lymphotropic virus type-2 (HTLV-2) is considered apathogenic and has been linked with benign lymphoproliferation and mild neurological symptoms in certain infected patients. The silencing of proviral gene expression and maintenance of latency are central for the establishment of persistent infections in vivo. The conserved pX sequences of HTLV-1 and HTLV-2 encode several ancillary factors which have been shown to negatively regulate proviral gene expression, while simultaneously activating host cellular proliferative and pro-survival pathways. In particular, the ORF-II proteins, HTLV-1 p30 and HTLV-2 p28, suppress Tax-dependent transactivation from the viral promoter-whereas p30 also inhibits PU.1-mediated inflammatory-signaling, differentially augments the expression of p53-regulated metabolic/pro-survival genes, and induces lymphoproliferation which could promote mitotic proviral replication. The ubiquitinated form of the HTLV-1 p13 protein localizes to nuclear speckles and interferes with recruitment of the p300 coactivator by the viral transactivator Tax. Further, the antisense-encoded HTLV-1 HBZ and HTLV-2 APH-2 proteins and mRNAs negatively regulate Tax-dependent proviral gene expression and activate inflammatory signaling associated with enhanced T-cell lymphoproliferation. This review will summarize our current understanding of the pX latency-maintenance factors of HTLV-1 and HTLV-2 and discuss how these products may contribute to the differences in pathogenicity between the human PTLVs.
Topics: Gene Expression Regulation, Viral; HTLV-I Infections; HTLV-II Infections; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Humans; Primate T-lymphotropic virus 1; Retroviridae Proteins, Oncogenic; Transcription Factors; Viral Regulatory and Accessory Proteins; Virus Latency
PubMed: 31492165
DOI: 10.1186/s12977-019-0487-9 -
Viruses Apr 2023Retroviruses, especially the pathogenic human immunodeficiency virus type 1 (HIV-1), have severely threatened human health for decades. Retroviruses can form stable... (Review)
Review
Retroviruses, especially the pathogenic human immunodeficiency virus type 1 (HIV-1), have severely threatened human health for decades. Retroviruses can form stable latent reservoirs via retroviral DNA integration into the host genome, and then be temporarily transcriptional silencing in infected cells, which makes retroviral infection incurable. Although many cellular restriction factors interfere with various steps of the life cycle of retroviruses and the formation of viral latency, viruses can utilize viral proteins or hijack cellular factors to evade intracellular immunity. Many post-translational modifications play key roles in the cross-talking between the cellular and viral proteins, which has greatly determined the fate of retroviral infection. Here, we reviewed recent advances in the regulation of ubiquitination and SUMOylation in the infection and latency of retroviruses, focusing on both host defense- and virus counterattack-related ubiquitination and SUMOylation system. We also summarized the development of ubiquitination- and SUMOylation-targeted anti-retroviral drugs and discussed their therapeutic potential. Manipulating ubiquitination or SUMOylation pathways by targeted drugs could be a promising strategy to achieve a "sterilizing cure" or "functional cure" of retroviral infection.
Topics: Humans; Sumoylation; Ubiquitination; Retroviridae Infections; Viral Proteins; Retroviridae
PubMed: 37112965
DOI: 10.3390/v15040985