Antisense Oligonucleotide-Based Therapy of Viral Infections

Nucleic acid-based therapeutics have demonstrated their efficacy in the treatment of various diseases and vaccine development. Antisense oligonucleotide (ASO) technology exploits a single-strand short oligonucleotide to either cause target RNA degradation or sterically block the binding of cellular factors or machineries to the target RNA. Chemical modification or bioconjugation of ASOs can enhance both its pharmacokinetic and pharmacodynamic performance, and it enables customization for a specific clinical purpose. ASO-based therapies have been used for treatment of genetic disorders, cancer and viral infections. In particular, ASOs can be rapidly developed for newly emerging virus and their reemerging variants. This review discusses ASO modifications and delivery options as well as the design of antiviral ASOs. A better understanding of the viral life cycle and virus-host interactions as well as advances in oligonucleotide technology will benefit the development of ASO-based antiviral therapies.

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The rabbit papillomavirus model: a valuable tool to study viral–host interactions

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2018.0294 ◽

2019 ◽

Vol 374 (1773) ◽

pp. 20180294 ◽

Cited By ~ 4

Author(s):

Nancy M. Cladel ◽

Xuwen Peng ◽

Neil Christensen ◽

Jiafen Hu

Keyword(s):

Viral Infections ◽

Vaccine Development ◽

Therapeutic Vaccine ◽

Rabbit Model ◽

Preclinical Model ◽

Sylvilagus Floridanus ◽

Host Interactions ◽

Cottontail Rabbit ◽

Transgenic Rabbits ◽

Viral Host Interactions

Cottontail rabbit papillomavirus (CRPV) was the first DNA virus shown to be tumorigenic. The virus has since been renamed and is officially known as Sylvilagus floridanus papillomavirus 1 (SfPV1). Since its inception as a surrogate preclinical model for high-risk human papillomavirus (HPV) infections, the SfPV1/rabbit model has been widely used to study viral–host interactions and has played a pivotal role in the successful development of three prophylactic virus-like particle vaccines. In this review, we will focus on the use of the model to gain a better understanding of viral pathogenesis, gene function and host immune responses to viral infections. We will discuss the application of the model in HPV-associated vaccine testing, in therapeutic vaccine development (using our novel HLA-A2.1 transgenic rabbits) and in the development and validation of novel anti-viral and anti-tumour compounds. Our goal is to demonstrate the role the SfPV1/rabbit model has played, and continues to play, in helping to unravel the intricacies of papillomavirus infections and to develop tools to thwart the disease. This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.

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Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Vaccines ◽

10.3390/vaccines8020302 ◽

2020 ◽

Vol 8 (2) ◽

pp. 302 ◽

Cited By ~ 1

Author(s):

Anthony C. Ike ◽

Chisom J. Onu ◽

Chukwuebuka M. Ononugbo ◽

Eleazar E. Reward ◽

Sophia O. Muo

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Viral Infections ◽

Recombinant Dna ◽

Vaccine Development ◽

The Body ◽

Effective Vaccine ◽

Subunit Vaccines ◽

Simplex Virus ◽

Hsv Infections

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

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Plasmodium knowlesi: a relevant, versatile experimental malaria model

Parasitology ◽

10.1017/s0031182016002286 ◽

2016 ◽

Vol 145 (1) ◽

pp. 56-70 ◽

Cited By ~ 8

Author(s):

ERICA M. PASINI ◽

ANNE-MARIE ZEEMAN ◽

ANNEMARIE VOORBERG-VAN DER WEL ◽

CLEMENS H. M. KOCKEN

Keyword(s):

Parasite Species ◽

Vaccine Development ◽

Plasmodium Knowlesi ◽

Host Interactions ◽

Model Studies ◽

Human Red Blood Cells ◽

Malaria Model ◽

Human Primate

SUMMARYThe primate malariaPlasmodium knowlesihas a long-standing history as an experimental malaria model. Studies using this model parasite in combination with its various natural and experimental non-human primate hosts have led to important advances in vaccine development and in our understanding of malaria invasion, immunology and parasite–host interactions. The adaptation to long-termin vitrocontinuous blood stage culture in rhesus monkey,Macaca fascicularisand human red blood cells, as well as the development of various transfection methodologies has resulted in a highly versatile experimental malaria model, further increasing the potential of what was already a very powerful model. The growing evidence thatP. knowlesiis an important human zoonosis in South-East Asia has added relevance to former and future studies of this parasite species.

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The evidence of porcine hemagglutinating encephalomyelitis virus induced nonsuppurative encephalitis as the cause of death in piglets

PeerJ ◽

10.7717/peerj.2443 ◽

2016 ◽

Vol 4 ◽

pp. e2443 ◽

Cited By ~ 24

Author(s):

Zi Li ◽

Wenqi He ◽

Yungang Lan ◽

Kui Zhao ◽

Xiaoling Lv ◽

...

Keyword(s):

Nervous System ◽

Cause Of Death ◽

Viral Infections ◽

Vaccine Development ◽

Wild Strain ◽

Effective Vaccine ◽

Symptoms Of Depression ◽

Encephalomyelitis Virus ◽

Cns Dysfunction ◽

Porcine Hemagglutinating Encephalomyelitis Virus

An acute outbreak of porcine hemagglutinating encephalomyelitis virus (PHEV) infection in piglets, characterized with neurological symptoms, vomiting, diarrhea, and wasting, occurred in China. Coronavirus-like particles were observed in the homogenized tissue suspensions of the brain of dead piglets by electron microscopy, and a wild PHEV strain was isolated, characterized, and designated as PHEV-CC14. Histopathologic examinations of the dead piglets showed characteristics of non-suppurative encephalitis, and some neurons in the cerebral cortex were degenerated and necrotic, and neuronophagia. Similarly, mice inoculated with PHEV-CC14 were found to have central nervous system (CNS) dysfunction, with symptoms of depression, arched waists, standing and vellicating front claws. Furthmore, PHEV-positive labeling of neurons in cortices of dead piglets and infected mice supported the viral infections of the nervous system. Then, the major structural genes of PHEV-CC14 were sequenced and phylogenetically analyzed, and the strain shared 95%–99.2% nt identity with the other PHEV strains available in GenBank. Phylogenetic analysis clearly proved that the wild strain clustered into a subclass with a HEV-JT06 strain. These findings suggested that the virus had a strong tropism for CNS, in this way, inducing nonsuppurative encephalitis as the cause of death in piglets. Simultaneously, the predicted risk of widespread transmission showed a certain variation among the PHEV strains currently circulating around the world. Above all, the information presented in this study can not only provide good reference for the experimental diagnosis of PHEV infection for pig breeding, but also promote its new effective vaccine development.

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Virus–Host Interactions: Viral Infections

10.5005/jp/books/12697_55 ◽

2016 ◽

pp. 392-392

Author(s):

Surinder Kumar

Keyword(s):

Viral Infections ◽

Host Interactions

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Hepatitis-Associated Glomerulonephritis

Kidney Protection ◽

10.1093/med/9780190611620.003.0039 ◽

2019 ◽

pp. 389-396

Author(s):

Julie Belliere ◽

Stanislas Faguer ◽

Nassim Kamar

Keyword(s):

Membranoproliferative Glomerulonephritis ◽

Hepatitis A ◽

Viral Infections ◽

Kidney Injury ◽

Hepatitis E ◽

Common Type ◽

Viral Clearance ◽

Antiviral Therapies ◽

Immune Phenomena ◽

Membranous Nephritis

Viral hepatitis can be associated with extrahepatic manifestations, including kidney injury, mainly glomerulonephritis (GN). The physiopathology of GN is of particular interest because some immune responses, triggered by viral infections, can harm the glomerulus, either via deposition of immune complexes, auto-immune phenomena, or through cytopathogenic effects. This chapter describes the epidemiology of hepatitis A-, B-, C-, and E-associated GN; the clinical and biological presentations; the histological patterns; and management regimens. Few cases of hepatitis A- or hepatitis E-associated GN have been reported. Cryoglobulinemic membranoproliferative glomerulonephritis is the most common type of GN diagnosed in patients infected by the hepatitis C virus. Patients infected by hepatitis B mainly develop membranous nephritis. Viral clearance using antiviral therapies, when available, is necessary to improve kidney outcomes.

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COVID-19: Current Developments and Further Opportunities in Drug Delivery and Therapeutics

Pharmaceutics ◽

10.3390/pharmaceutics12100945 ◽

2020 ◽

Vol 12 (10) ◽

pp. 945

Author(s):

Saman Zafar ◽

Muhammad Sohail Arshad ◽

Sameen Fatima ◽

Amna Ali ◽

Aliyah Zaman ◽

...

Keyword(s):

Drug Delivery ◽

Vaccine Development ◽

Viral Vector ◽

Age Groups ◽

World Health ◽

Disease Spread ◽

Plasma Therapy ◽

Antiviral Therapies ◽

Health Organization ◽

Spread Of Infection

SARS-CoV-2 has affected people from all age groups, races and ethnicities. Given that many infected individuals are asymptomatic, they transmit the disease to others unknowingly, which has resulted in the spread of infection at an alarming rate. This review aims to provide an overview of the pathophysiology, preventive measures to reduce the disease spread, therapies currently in use, an update on vaccine development and opportunities for vaccine delivery. The World Health Organization has advised several precautions including social distancing, hand washing and the use of PPE including gloves and face masks for minimizing the spread of SARS-CoV-2 infection. At present, several antiviral therapies previously approved for other infections are being repositioned to study their efficacy against SARS-CoV-2. In addition, some medicines (i.e., remdesivir, chloroquine, hydroxychloroquine) have received emergency use authorisation from the FDA. Plasma therapy has also been authorised for emergency use for the treatment of COVID-19 on a smaller scale. However, no vaccine has been approved so far against this virus. Nevertheless, several potential vaccine targets have been reported, and development of different types of vaccines including DNA, mRNA, viral vector, inactivated, subunit and vaccine-like particles is in process. It is concluded that a suitable candidate delivered through an advanced drug delivery approach would effectively boost the immune system against this coronavirus.

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Single-Cell Analysis Reveals Heterogeneity of Virus Infection, Pathogenicity, and Host Responses: HIV as a Pioneering Example

Annual Review of Virology ◽

10.1146/annurev-virology-021820-102458 ◽

2020 ◽

Vol 7 (1) ◽

pp. 333-350

Author(s):

Ludivine Brandt ◽

Sara Cristinelli ◽

Angela Ciuffi

Keyword(s):

Hiv Infection ◽

Single Cell ◽

Viral Infections ◽

Single Cell Analysis ◽

Host Responses ◽

Cell Analysis ◽

Host Interactions ◽

Immunodeficiency Virus ◽

Extreme Phenotypes ◽

Individual Consideration

While analyses of cell populations provide averaged information about viral infections, single-cell analyses offer individual consideration, thereby revealing a broad spectrum of diversity as well as identifying extreme phenotypes that can be exploited to further understand the complex virus-host interplay. Single-cell technologies applied in the context of human immunodeficiency virus (HIV) infection proved to be valuable tools to help uncover specific biomarkers as well as novel candidate players in virus-host interactions. This review aims at providing an updated overview of single-cell analyses in the field of HIV and acquired knowledge on HIV infection, latency, and host response. Although HIV is a pioneering example, similar single-cell approaches have proven to be valuable for elucidating the behavior and virus-host interplay in a range of other viruses.

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