Future Virol
· 2017 Jun · PMID 36776482
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Adeno-associated viruses (AAVs) are promising therapeutic viral vectors. Their capsid is assembled from viral proteins VP1, VP2 and VP3, aided by an assembly-activating protein, followed by replication protein mediated p...Adeno-associated viruses (AAVs) are promising therapeutic viral vectors. Their capsid is assembled from viral proteins VP1, VP2 and VP3, aided by an assembly-activating protein, followed by replication protein mediated packaging of their 4.7-kb genome with inverted terminal repeats as packaging signals. To aid improvement of AAV vectors, knowledge of viral determinants of successful capsid assembly and genome packaging is important. We review the current knowledge of these two processes and efforts to overcome limited DNA packaging capacity and limit the packaging of unwanted foreign DNA in vector development. Residues involved in essential capsid assembly and genome packaging interactions cannot be manipulated in vector engineering. This information thus aids strategies to improve vector production and to increase AAV packaging capacity toward improved efficacy of this vector system.
Rimawi BH, Smith SL, Badell ML
… +4 more, Zahedi-Spung LD, Sheth AN, Haddad L, Chakraborty R
Future Virol
· 2016 Aug · PMID 28348636
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Linkage and retention in care for many HIV-infected women in the postpartum period is suboptimal, which compromises long-term virologic suppression and the HIV Care Continuum. Efforts are needed to improve individual out...Linkage and retention in care for many HIV-infected women in the postpartum period is suboptimal, which compromises long-term virologic suppression and the HIV Care Continuum. Efforts are needed to improve individual outcomes by addressing transitions in care. We summarize some successful strategies to engage and retain HIV-infected women in care during the postpartum period.
Future Virol
· 2017 Mar · PMID 29937918
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Dengue is a worldwide disease with 400 million annual infections that can lead to septic shock and viral hemorrhagic fever with internal bleeding. These symptoms are the result of uncontrolled immune activation. Macropha...Dengue is a worldwide disease with 400 million annual infections that can lead to septic shock and viral hemorrhagic fever with internal bleeding. These symptoms are the result of uncontrolled immune activation. Macrophages and dendritic cells are the main target of dengue virus (DENV) and the cellular source of cytokines associated with this immune activation. Macrophages and dendritic cells express several innate immune receptors that have been implicated in DENV immune activation, of which, CLEC5A, RIG-I and MDA5 are most important. Notably, activation of these receptors have profound effects on adaptive immune responses against DENV. This review will focus on how innate immune receptors drive DENV immune activation by inducing inflammatory cytokines and by activating adaptive immune responses.
Future Virol
· 2016 Oct · PMID 27840654
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As of May 2016, 81 countries have introduced Rotarix or RotaTeq rotavirus vaccines into their national immunization program. Despite initially slow uptake in some countries and differences in vaccine effectiveness (VE) b...As of May 2016, 81 countries have introduced Rotarix or RotaTeq rotavirus vaccines into their national immunization program. Despite initially slow uptake in some countries and differences in vaccine effectiveness (VE) between high-, low- and middle-income countries, impact of the vaccines has been swift and striking in all settings, with good VE against vaccine-type and nonvaccine-type strains. Newly published research indicates poor nutrition is associated with decreased VE and breastfeeding at the time of vaccination does not affect vaccine response. Vaccines in development and proposed alternate schedules also promise to address limitations of the current vaccines and optimize rotavirus disease prevention.
Morris SJ, Sebastian S, Spencer AJ
… +1 more, Gilbert SC
Future Virol
· 2016 Sep · PMID 29527232
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Replication incompetent human adenovirus serotype 5 (HAdV-C5) has been extensively used as a delivery vehicle for gene therapy proteins and infectious disease antigens. These vectors infect replicating and nonreplicating...Replication incompetent human adenovirus serotype 5 (HAdV-C5) has been extensively used as a delivery vehicle for gene therapy proteins and infectious disease antigens. These vectors infect replicating and nonreplicating cells, have a broad tissue tropism, elicit high immune responses and are easily purified to high titers. However, the utility of HAdV-C5 vectors as potential vaccines is limited due to pre-existing immunity within the human population that significantly reduces the immunogenicity of HAdV-C5 vaccines. In recent years, adenovirus vaccine development has focused on simian-derived adenoviral vectors, which have the desirable vector characteristics of HAdV-C5 but with negligible seroprevalence in the human population. Here, we discuss recent advances in simian adenovirus vaccine vector development and evaluate current research specifically focusing on clinical trial data.
Future Virol
· 2016 Jul · PMID 32201496
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Recently, two coronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, have emerged to cause unusually severe respiratory disease in humans. Currently, there is a lac...Recently, two coronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, have emerged to cause unusually severe respiratory disease in humans. Currently, there is a lack of effective antiviral treatment options or vaccine available. Given the severity of these outbreaks, and the possibility of additional zoonotic coronaviruses emerging in the near future, the exploration of different treatment strategies is necessary. Disease resilience is the ability of a given host to tolerate an infection, and to return to a state of health. This review focuses on exploring various host resilience mechanisms that could be exploited for treatment of severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and other respiratory viruses that cause acute lung injury and acute respiratory distress syndrome.
Everts M, Suto MJ, Painter GR
… +1 more, Whitley RJ
Future Virol
· 2016 Mar · PMID 27325914
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Viral infections, such as Ebola, severe acute respiratory syndrome/Middle East respiratory syndrome and West Nile virus have emerged as a serious health threat with no effective therapies. These infections have little co...Viral infections, such as Ebola, severe acute respiratory syndrome/Middle East respiratory syndrome and West Nile virus have emerged as a serious health threat with no effective therapies. These infections have little commercial potential and are not a high priority for the pharmaceutical industry. However, the academic community has been active in this area for many years. The challenge is how to take this academic virology knowledge into a drug discovery and development domain. One approach is the use of consortia and public-private partnerships this article highlights ongoing efforts in the USA. Public funds, such as those from government sources, can support research efforts that do not to appear to have commercial value. The key to success is finding a way to combine the different cultural and operational values and reward systems into a productive collaboration to identify new antivirals.
Future Virol
· 2015 Oct · PMID 27066105
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HSV type-1 and -2 are widespread pathogens producing lifelong infection with multiple sequelae, including oral, ocular and genital disease. The process of herpesvirus entry is a highly complex process involving numerous...HSV type-1 and -2 are widespread pathogens producing lifelong infection with multiple sequelae, including oral, ocular and genital disease. The process of herpesvirus entry is a highly complex process involving numerous viral and cellular factors. Entry begins with attachment of virus to the cell surface followed by interactions between viral glycoproteins and cellular receptors to facilitate capsid penetration. The nucleocapsid is then transported along microtubules to the nuclear membrane, where viral DNA is released for replication in the nucleus. The work reviewed here comprises the most recent advancements in our understanding of the mechanism involved in the herpesvirus entry process.
Chronic hepatitis C virus (HCV) is a global epidemic, affecting approximately 150 million individuals throughout the world. The implications of HCV infection have been magnified in those who are infected with both HCV an...Chronic hepatitis C virus (HCV) is a global epidemic, affecting approximately 150 million individuals throughout the world. The implications of HCV infection have been magnified in those who are infected with both HCV and the HIV as liver disease progression, liver failure and liver-related death are increased, particularly in those without well-controlled HIV disease. The development of direct-acting antiviral agents for HCV that allow shorter treatment periods with increased efficacy and decreased adverse events have greatly changed the outlook for HCV-infected individuals. With these advancements, growing treatment options for the coinfected population have also come. This review will address pharmacotherapy issues in the HIV/HCV coinfected population.
Glycoproteins are critical to virus entry, to spread within and between hosts and can modify the behavior of cells. Many viruses carry only a few, most found in the virion envelope. EBV makes more than 12, providing flex...Glycoproteins are critical to virus entry, to spread within and between hosts and can modify the behavior of cells. Many viruses carry only a few, most found in the virion envelope. EBV makes more than 12, providing flexibility in how it colonizes its human host. Some are dedicated to getting the virus through the cell membrane and on toward the nucleus of the cell, some help guide the virus back out and on to the next cell in the same or a new host. Yet others undermine host defenses helping the virus persist for a lifetime, maintaining a presence that is mostly tolerated and serves to perpetuate EBV as one of the most common infections of man.
Highly pathogenic influenza viruses of the H5N1 subtype have infected more than 600 people since 1997, resulting in the deaths of approximately 60% of those infected. Multiple studies have established the viral hemagglut...Highly pathogenic influenza viruses of the H5N1 subtype have infected more than 600 people since 1997, resulting in the deaths of approximately 60% of those infected. Multiple studies have established the viral hemagglutinin (HA) surface glycoprotein as the major determinant of H5N1 virulence. HA mediates host-specific virus binding to cells, and mutations that allow efficient binding to viral receptors on mammalian cells are critical (although not sufficient) for H5N1 transmissibility among mammals. The viral polymerase PB2 protein is also a critical virulence determinant, and adaptive mutations in this protein are crucial for efficient H5N1 virus replication in mammals. Additionally, viral proteins (such as NS1 and PB1-F2) with roles in innate immune responses also affect the virulence of highly pathogenic H5N1 viruses.
Antimicrobial resistance is a serious healthcare concern affecting millions of people around the world. Antiviral resistance has been viewed as a lesser threat than antibiotic resistance, but it is important to consider...Antimicrobial resistance is a serious healthcare concern affecting millions of people around the world. Antiviral resistance has been viewed as a lesser threat than antibiotic resistance, but it is important to consider approaches to address this growing issue. While vaccination is a logical strategy, and has been shown to be successful many times over, next generation viral vaccines with a specific goal of curbing antiviral resistance will need to clear several hurdles including vaccine design, evaluation and implementation. This article suggests that a new model of vaccination may need to be considered: rather than focusing on public health, this model would primarily target sectors of the population who are at high risk for complications from certain infections.
Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on glo...Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration.
Human noroviruses (HuNoVs) are a leading cause of acute, nonbacterial gastroenteritis worldwide. The lack of a cell culture system and smaller animal model has delayed the development and commercial availability of vacci...Human noroviruses (HuNoVs) are a leading cause of acute, nonbacterial gastroenteritis worldwide. The lack of a cell culture system and smaller animal model has delayed the development and commercial availability of vaccines and antiviral drugs. Current vaccines rely on recombinant capsid proteins, such as P particles and virus-like particles (VLPs), which have been promising in clinical trials. Anti-HuNoV drug development is another area of extensive research, including currently available antiviral drugs for other viral pathogens. This review will provide an overview of recent advances in vaccine and antiviral development. The implication of recent advances in HuNoV cell culture for improving vaccine and antiviral development is also discussed.
Future Virol
· 2015 Jul · PMID 26478738
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Infants with respiratory syncytial virus (RSV) lower respiratory tract infections (LRIs) are at increased risk for childhood asthma. The objectives of this article are to review the genes associated with both RSV LRI and...Infants with respiratory syncytial virus (RSV) lower respiratory tract infections (LRIs) are at increased risk for childhood asthma. The objectives of this article are to review the genes associated with both RSV LRI and asthma, review analytic approaches to assessing shared genetic risk and propose a future perspective on how these approaches can help us to understand the role of infant RSV infection as both an important risk factor for asthma and marker of shared genetic etiology between the two conditions. The review of shared genes and thus pathways associated with severity of response to RSV infection and asthma risk can help us to understand mechanisms of disease and ultimately propose new and novel targets for primary prevention of both diseases.
Bioluminescence imaging (BLI) has emerged as a powerful tool in the study of animal models of viral disease. BLI enables real-time study of viral infection, host immune response and the efficacy of intervention strategi...Bioluminescence imaging (BLI) has emerged as a powerful tool in the study of animal models of viral disease. BLI enables real-time study of viral infection, host immune response and the efficacy of intervention strategies. Substrate dependent light emitting luciferase enzyme when incorporated into a virus as a reporter gene enables detection of bioluminescence from infected cells using sensitive charge-coupled device (CCD) camera systems. Advantages of BLI include low background, real-time tracking of infection in the same animal and reduction in the requirement for larger animal numbers. Transgenic luciferase-tagged mice enable the use of pre-existing nontagged viruses in BLI studies. Continued development in luciferase reporter genes, substrates, transgenic animals and imaging systems will greatly enhance future BLI strategies in viral research.