Future Virol
· 2018 Dec · PMID 34079586
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The oncogenic potential of Epstein-Barr virus (EBV) is mostly attributed to latent membrane protein 1 (LMP1), which is essential and sufficient for transformation of fibroblast and primary lymphocytes. LMP1 expression re...The oncogenic potential of Epstein-Barr virus (EBV) is mostly attributed to latent membrane protein 1 (LMP1), which is essential and sufficient for transformation of fibroblast and primary lymphocytes. LMP1 expression results in the activation of multiple signaling cascades like NF-ΚB and MAP kinases that trigger cell survival and proliferative pathways. LMP1 specific signaling events are mediated through the recruitment of a number of interacting proteins to various signaling domains. Based on these properties, LMP1 is an attractive target to develop effective therapeutics to treat EBV-related malignancies. In this review, we focus on LMP1 interacting proteins, associated signaling events, and potential targets that could be exploited for therapeutic strategies.
Future Virol
· 2018 Sep · PMID 30416535
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Oncolytic viruses (OVs) do more than simply infect and kill host cells. The accepted mechanism of action for OVs consists of a primary lytic phase and a subsequent antitumor and antiviral immune response. However, not al...Oncolytic viruses (OVs) do more than simply infect and kill host cells. The accepted mechanism of action for OVs consists of a primary lytic phase and a subsequent antitumor and antiviral immune response. However, not all cells are subject to the direct effects of OV therapy, and it is becoming clear that OVs can also impact uninfected cells in the periphery. This review discusses the effects of OVs on uninfected neighboring cells, so-called bystander effects, and implications for OV therapies alone or in combination with other standard of care chemotherapy.
Future Virol
· 2018 Nov · PMID 34367314
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Epstein-Barr Virus (EBV) was the first discovered human tumor virus and is the etiological agent of B cell lymphomas and also epithelial cancers. Indeed, nearly 10% of gastric cancers worldwide are EBV-positive and displ...Epstein-Barr Virus (EBV) was the first discovered human tumor virus and is the etiological agent of B cell lymphomas and also epithelial cancers. Indeed, nearly 10% of gastric cancers worldwide are EBV-positive and display unique molecular, epigenetic, and clinicopathological features. EBV-positive gastric cancers display the highest rate of host genome methylation of all tumor types studied and harbor recurrent mutations activating PI3Kα, silencing ARID1A, and amplifying PD-L1. While EBV infection of B cells can be studied efficiently, epithelial cell infection is much more difficult. We propose that new culture models including 3D-based gastric organoids and xenografts can bring new insight into EBV-induced gastric carcinogenesis and will lead to improved precision medicine-based therapies for patients with EBV-positive gastric cancer.
Future Virol
· 2018 Jul · PMID 30245735
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Human rhinoviruses are the primary etiological agent of the common cold. This infection can be mild and self-limiting in immunocompetent hosts, but can be associated with bronchiolitis in infants, pneumonia in the immuno...Human rhinoviruses are the primary etiological agent of the common cold. This infection can be mild and self-limiting in immunocompetent hosts, but can be associated with bronchiolitis in infants, pneumonia in the immunosuppressed and exacerbations of pre-existing pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Many of these conditions can place significant economic costs upon healthcare infrastructure. There is currently no licensed vaccine for rhinovirus, as the large variety of rhinovirus serotypes has posed significant challenges for research. In this review, we discuss current knowledge around antiviral drugs and small molecule inhibitors of rhinovirus infection, as well as antiviral host defense peptides as exciting prospects to approach the development of novel therapeutics which target human rhinovirus.
Future Virol
· 2018 Jul · PMID 30245734
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Defective viral genomes (DVGs) are natural products of virus replication that occur in many positive and negative sense RNA viruses, including Ebola, dengue and respiratory syncytial virus. DVGs, which have severe genomi...Defective viral genomes (DVGs) are natural products of virus replication that occur in many positive and negative sense RNA viruses, including Ebola, dengue and respiratory syncytial virus. DVGs, which have severe genomic truncations and require a helper virus to replicate, have three well-described functions: interference with standard virus replication, immunostimulation, and establishment of virus persistence. These functions of DVGs were first described almost 50 years ago, yet only recent studies have shown the molecular intersection between their immunostimulatory and pro-persistence activities. Here, we review more than half a century of scientific literature on the immunostimulatory and pro-persistence functions of DVGs. We highlight recent advances in the field and the critical role DVGs have in both the acute and long-term virus-host interactions.
Future Virol
· 2018 Jul · PMID 30245733
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AIM: The goal of this study was to determine if a single AAV vector, encoding Cas9 and guide RNAs specific for the HPV16 E6 and E7 genes, could inhibit the growth of an HPV16-induced tumor . MATERIALS & METHODS: We grew...AIM: The goal of this study was to determine if a single AAV vector, encoding Cas9 and guide RNAs specific for the HPV16 E6 and E7 genes, could inhibit the growth of an HPV16-induced tumor . MATERIALS & METHODS: We grew HPV16, patient-derived anal cancer explants in immunodeficient mice and then challenged these by injection of AAV-based vectors encoding Cas9 and control or HPV16-specific guide RNAs. RESULTS & CONCLUSION: We observed a significant and selective reduction in tumor growth when the HPV16 E6 and E7 genes were targeted using Cas9. These studies provide proof of principle for the hypothesis that CRISPR/Cas has the potential to be used to selectively treat HPV-induced tumors in humans.
Future Virol
· 2018 Aug · PMID 33598044
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AIM: Assess risks related to breaches of poliovirus containment. METHOD: Using a dynamic transmission model, we explore the variability among different populations in the vulnerability to poliovirus containment breaches...AIM: Assess risks related to breaches of poliovirus containment. METHOD: Using a dynamic transmission model, we explore the variability among different populations in the vulnerability to poliovirus containment breaches as population immunity to transmission declines after oral poliovirus vaccine (OPV) cessation. RESULTS: Although using OPV instead of wild poliovirus (WPV) seed strains for inactivated poliovirus vaccine (IPV) production offers some expected risk reintroduction of live polioviruses from IPV manufacturing facilities, OPV seed strain releases may become a significant threat within 5-10 years of OPV cessation in areas most conducive to fecal-oral poliovirus transmission, regardless of IPV use. CONCLUSIONS: Efforts to quantify the risks demonstrate the challenges associated with understanding and managing relatively low-probability and high-consequence containment failure events.
Future Virol
· 2018 Aug · PMID 32201498
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Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which can be activated by cytokines, growth factor receptors, and nonreceptor-like tyrosine kinase. An activated STAT3 translocates int...Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which can be activated by cytokines, growth factor receptors, and nonreceptor-like tyrosine kinase. An activated STAT3 translocates into the nucleus and combines with DNA to regulate the expression of target genes involved in cell proliferation, differentiation, apoptosis and metastasis. Recent studies have shown that STAT3 plays important roles in viral infection and pathogenesis. STAT3 exhibits a proviral function in several viral infections, including those of HBV, HCV, HSV-1, varicella zoster virus, human CMV and measles virus. However, in some circumstances, STAT3 has an antiviral function in other viral infections, such as enterovirus 71, severe acute respiratory syndrome coronavirus and human metapneumovirus. This review summarizes the roles of STAT3 in viral infection and pathogenesis, and briefly discusses the molecular mechanisms involved in these processes.
Future Virol
· 2018 May · PMID 29967651
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Alpha herpesviruses are common pathogens of mammals. They establish a productive infection in many cell types, but a life-long latent infection occurs in PNS neurons. A vast majority of the human population has latent HS...Alpha herpesviruses are common pathogens of mammals. They establish a productive infection in many cell types, but a life-long latent infection occurs in PNS neurons. A vast majority of the human population has latent HSV-1 infections. Currently, there is no cure to clear latent infections. Even though HSV-1 is among the best studied viral pathogens, regulation of latency and reactivation is not well understood due to several challenges including a lack of animal models that precisely recapitulate latency/reactivation episodes; a difficulty in modeling latency; and a limited understanding of neuronal biology. In this review, we discuss insights gained from latency models with a focus on the neuronal and viral factors that determine the mode of infection.
Future Virol
· 2018 May · PMID 29967650
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Nucleotide sequences of HIV isolates are obtained routinely to evaluate the presence of resistance mutations to antiretroviral drugs. But, beyond their clinical use, these and other viral sequences include a wealth of in...Nucleotide sequences of HIV isolates are obtained routinely to evaluate the presence of resistance mutations to antiretroviral drugs. But, beyond their clinical use, these and other viral sequences include a wealth of information that can be used to better understand and characterize the epidemiology of HIV in relevant populations. In this review, we provide a brief overview of the main methods used to analyze HIV sequences, the data bases where reference sequences can be obtained, and some caveats about the possible applications for public health of these analyses, along with some considerations about their limitations and correct usage to derive robust and reliable conclusions.
Future Virol
· 2018 Jun · PMID 32201497
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Post-translational modifications (PTMs) refer to the covalent modifications of polypeptides after they are synthesized, adding temporal and spatial regulation to modulate protein functions. Being obligate intracellular p...Post-translational modifications (PTMs) refer to the covalent modifications of polypeptides after they are synthesized, adding temporal and spatial regulation to modulate protein functions. Being obligate intracellular parasites, viruses rely on the protein synthesis machinery of host cells to support replication, and not surprisingly, many viral proteins are subjected to PTMs. Coronavirus (CoV) is a group of enveloped RNA viruses causing diseases in both human and animals. Many CoV proteins are modified by PTMs, including glycosylation and palmitoylation of the spike and envelope protein, N- or O-linked glycosylation of the membrane protein, phosphorylation and ADP-ribosylation of the nucleocapsid protein, and other PTMs on nonstructural and accessory proteins. In this review, we summarize the current knowledge on PTMs of CoV proteins, with an emphasis on their impact on viral replication and pathogenesis. The ability of some CoV proteins to interfere with PTMs of host proteins will also be discussed.
Future Virol
· 2018 Mar · PMID 29750084
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Viruses alter host-cell gene expression at many biochemical levels, such as transcription, translation, mRNA splicing and mRNA decay in order to create a cellular environment suitable for viral replication. In this revie...Viruses alter host-cell gene expression at many biochemical levels, such as transcription, translation, mRNA splicing and mRNA decay in order to create a cellular environment suitable for viral replication. In this review, we discuss mechanisms by which viruses manipulate host-gene expression at the level of mRNA decay in order to enable the virus to evade host antiviral responses to allow viral survival and replication. We discuss different cellular RNA decay pathways, including the deadenylation-dependent mRNA decay pathway, and various strategies that viruses exploit to manipulate these pathways in order to create a virus-friendly cellular environment.
Maroun J, Muñoz-Alía M, Ammayappan A
… +3 more, Schulze A, Peng KW, Russell S
Future Virol
· 2017 Apr · PMID 29387140
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Oncolytic viruses (OVs) are engineered and/or evolved to propagate selectively in cancerous tissues. They have a dual mechanism of action; direct killing of infected cancer cells cross-primes anticancer immunity to boost...Oncolytic viruses (OVs) are engineered and/or evolved to propagate selectively in cancerous tissues. They have a dual mechanism of action; direct killing of infected cancer cells cross-primes anticancer immunity to boost the killing of uninfected cancer cells. The goal of the field is to develop OVs that are easily manufactured, efficiently delivered to disseminated sites of cancer growth, undergo rapid intratumoral spread, selectively kill tumor cells, cause no collateral damage and pose no risk of transmission in the population. Here we discuss the many virus engineering strategies that are being pursued to optimize delivery, intratumoral spread and safety of OVs derived from different virus families. With continued progress, OVs have the potential to transform the paradigm of cancer care.
Future Virol
· 2017 Sep · PMID 29225661
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To systematically review the association between maternal nutritional status in pregnancy and infant immune response to childhood vaccines. We reviewed literature on maternal nutrition during pregnancy, fetal immune syst...To systematically review the association between maternal nutritional status in pregnancy and infant immune response to childhood vaccines. We reviewed literature on maternal nutrition during pregnancy, fetal immune system and vaccines and possible relationships. Thereafter, we undertook a systematic review of the literature of maternal nutritional status and infant vaccine response, extracted relevant information, assessed quality of the nine papers identified and present findings in a narrative format. From limited evidence of average quality, intrauterine nutrition deficiency could lead to functional deficit in the infant's immune function; child vaccine response may thus be negatively affected by maternal malnutrition. Response to childhood vaccination may be associated with fetal and early life environment; evaluation of programs should take this into account.
Future Virol
· 2017 Nov · PMID 29181086
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Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to sub-Saharan Africa and the Arabian Peninsula and the etiological agent of Rift Valley fever. Rift Valley fever is a disease of major public health...Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to sub-Saharan Africa and the Arabian Peninsula and the etiological agent of Rift Valley fever. Rift Valley fever is a disease of major public health and economic concern, affecting livestock and humans. In ruminants, RVFV infection is characterized by high mortality rates in newborns and near 100% abortion rates in pregnant animals. Infection in humans is typically manifested as a self-limiting febrile illness, but can lead to severe and fatal hepatitis, encephalitis, hemorrhagic fever or retinitis with partial or complete blindness. Currently, there are no specific treatment options available for RVFV infection. This review presents a summary of the therapeutic approaches that have been explored on the treatment of RVFV infection.
Future Virol
· 2017 May · PMID 28919920
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West Nile virus (WNV), a neurotropic mosquito-borne flavivirus, has become endemic in the USA and parts of Europe since 1999. There is no licensed WNV vaccine for humans. Considering the robust immunity from immunization...West Nile virus (WNV), a neurotropic mosquito-borne flavivirus, has become endemic in the USA and parts of Europe since 1999. There is no licensed WNV vaccine for humans. Considering the robust immunity from immunization with live, attenuated vaccines, a live WNV vaccine is an ideal platform for disease control. Animal and mosquito studies have identified a number of candidate attenuating mutations, including the structural proteins premembrane/membrane and envelope, and the nonstructural proteins NS1, NS2A, NS3, NS4A, NS4B and NS5, and the 3' UTR. Many of the mutations that have been examined attenuate WNV using different mechanisms, thus providing a greater understanding of WNV virulence while also identifying specific mutations as candidates to include in a WNV live vaccine.
Williamson V, Coetzee B, Kagee A
… +1 more, Tomlinson M
Future Virol
· 2017 Jan · PMID 28757895
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UNLABELLED: Despite advances in preventive treatments for HIV, children continue to become infected with HIV. Research has investigated adult and adolescents' willingness to participate in hypothetical HIV vaccine trials...UNLABELLED: Despite advances in preventive treatments for HIV, children continue to become infected with HIV. Research has investigated adult and adolescents' willingness to participate in hypothetical HIV vaccine trials; however, maternal willingness to enroll their infants in such trials remains underexplored. AIM: This study explored the factors influencing mothers' decision-making about enrolling their HIV negative infants in a hypothetical HIV vaccine trial. Methods: HIV infected and uninfected mothers (n = 22) were interviewed. RESULTS: Several factors were identified as influencing the mothers' decisions, including perceptions and knowledge of HIV and vaccines. CONCLUSION: Maternal concerns about protecting their infants from HIV were also identified and mothers indicated that they were eager to vaccinate their children. Insufficient information and reassurance regarding vaccine trial safety and efficacy influenced maternal reluctance to enroll their child.
Future Virol
· 2016 Dec · PMID 28757894
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More than 35 million people remain infected with HIV-1. Upon antiretroviral therapy cessation, HIV-1-positive individuals systematically fail to achieve sustained virological remission, revealing the presence of a reserv...More than 35 million people remain infected with HIV-1. Upon antiretroviral therapy cessation, HIV-1-positive individuals systematically fail to achieve sustained virological remission, revealing the presence of a reservoir. This reservoir takes into account anatomical sanctuaries where HIV-1 continues to replicate, and latently infected cells also known as the latent reservoir (LR). A better understanding of the nature and features of the LR and its quantification are crucial to evaluate the efficiency of therapeutic strategies aiming at purging HIV-1. Culture- and PCR-based assays have already been implemented to measure the LR, and new assays are continuously being developed. In this review, we will discuss these methods highlighting the difficulties to accurately measure the LR, one main obstacle in curing HIV-1.