The life cycle of the alphaviruses: From an antiviral perspective

Skidmore, Andrew M.; Bradfute, Steven B.

doi:10.1016/j.antiviral.2022.105476

Cited by 11 publications

(38 citation statements)

References 289 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, it is expected that the development of (2023) 9:17 16 0123456789();: Primer exceedingly safe antivirals will also enable their use as prophylactic treatment, for example, to be taken by travellers to endemic regions or household members of patients 294 . Several promising candidate drugs targeting the viral enzymatic functions have been reported, including new or nature-derived chemical compounds inhibiting the capping, macrodomain and capsid protease functions of nsPs [294][295][296] . However, none of these compounds has yet been tested in vivo or entered preclinical evaluation.…”

Section: Discussionmentioning

confidence: 99%

“…Targeting the viral entry pathway, and specifically targeting the viral envelope-MXRA8 receptor interaction using recombinant Fc-MXRA8 fragments or combinations of neutralizing monoclonal antibodies 300 , has shown promise in animal models, and these approaches have a low risk of off-target effects. Other therapeutic strategies being investigated involve targeting host cell pathways that support or suppress viral replication, including fatty acid synthesis and cholesterol trafficking pathways, dysregulation of endosome acidification to suppress virus entry, inhibition of nucleobase biosynthesis, or immunomodulatory therapies to stimulate an interferon response [294][295][296] . For promising broad-spectrum candidate compounds that show antiviral activity against several viruses, off-target toxic effects due to disruption of cellular pathways are to be expected; nevertheless, preclinical and clinical evaluations are still lacking 132,157, .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chikungunya fever

Bartholomeeusen

Daniel²,

LaBeaud

et al. 2023

Nat Rev Dis Primers

View full text Add to dashboard Cite

Chikungunya virus is widespread throughout the tropics, where it causes recurrent outbreaks of chikungunya fever. In recent years, outbreaks have afflicted populations in East and Central Africa, South America and Southeast Asia. The virus is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Chikungunya fever is characterized by severe arthralgia and myalgia that can persist for years and have considerable detrimental effects on health, quality of life and economic productivity. The effects of climate change as well as increased globalization of commerce and travel have led to growth of the habitat of Aedes mosquitoes. As a result, increasing numbers of people will be at risk of chikungunya fever in the coming years. In the absence of specific antiviral treatments and with vaccines still in development, surveillance and vector control are essential to suppress re-emergence Nature Reviews Disease Primers | (2023) 9:17 2 0123456789();: PrimerWith the increasing global distribution of the Aedes mosquitoes and their ability to adapt to urban settings, the urban transmission cycle is increasingly important. Here, during a blood meal on an infected person, the female mosquito ingests the virus, which infects various mosquito tissues, including the salivary glands. During a subsequent blood meal by the infected mosquito, the virus is deposited in the skin of an uninfected person along with mosquito saliva, infecting the person and perpetuating the viral replication cycle 14 . Phylogenetic analysis identified three distinct lineages corresponding to their respective geographical origin: West African, East Central South African (ECSA) and Asian lineage 15,16 . The ECSA lineage is further divided into two clades: ECSA1, which consists entirely of ancestral CHIKV sequences, and ECSA2, which contains sequences from the Central African Republic, Cameroon, Gabon and the Republic of Congo 17,18 . Since its discovery in 1952, CHIKV has been reported to be circulating and causing sporadic outbreaks in sub-Saharan Africa. In 2004, an ECSA CHIKV strain emerged in Kenya and subsequently spread to the Indian Ocean Islands, where it caused outbreaks of an unprecedented magnitude, particularly in La Réunion [19][20][21][22][23][24] . The extent of this outbreak has led to the emergence of a fourth phylogenetic lineage termed Indian Ocean lineage, which has subsequently dispersed to Asia and India 25 and caused autochthonous transmission (local disease spread) in Mediterranean Europe (Italy and France) 26,27 .In December 2013, another major outbreak occurred when a strain from the Asian lineage emerged for the first time on the Caribbean Saint Martin Island, from where the virus spread to more than 50 countries of the South American continent, causing a conservatively estimated 1 million infections 28,29 . In 2014, the ECSA lineage was reported in Northeast Brazil, where it continues to circulate as the most prevalent strain today 30 .Most of the Indian Ocean lineage is characterized by an adaptive mutation in the E1 glycopr...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chikungunya fever

Bartholomeeusen

Daniel²,

LaBeaud

et al. 2023

Nat Rev Dis Primers

View full text Add to dashboard Cite

show abstract

“…Later, Rep is processed, and its mature form amplifies the viral genome using the minus-sense genome as a template, and it also amplifies a smaller plus-sense RNA from a sub-genomic promoter located upstream of the second ORF. The subgenomic RNA also mimics an mRNA, and it is translated to produce a large structural polyprotein that will give rise to the viral capsid and envelope proteins [ 126 ].…”

Section: Viral Vectors To Deliver Immunomodulatory Antibodiesmentioning

confidence: 99%

Local Delivery of Immunomodulatory Antibodies for Gastrointestinal Tumors

Silva-Pilipich

Covo-Vergara

Smerdou

2023

Cancers

View full text Add to dashboard Cite

Cancer therapy has experienced a breakthrough with the use of immune checkpoint inhibitors (ICIs) based on monoclonal antibodies (mAbs), which are able to unleash immune responses against tumors refractory to other therapies. Despite the great advancement that ICIs represent, most patients with gastrointestinal tumors have not benefited from this therapy. In addition, ICIs often induce adverse effects that are related to their systemic use. Local administration of ICIs in tumors could concentrate their effect in the malignant tissue and provide a higher safety profile. A new and attractive approach for local delivery of ICIs is the use of gene therapy vectors to express these blocking antibodies in tumor cells. Several vectors have been evaluated in preclinical models of gastrointestinal tumors to express ICIs against PD-1, PD-L1, and CTLA-4, among other immune checkpoints, with promising results. Vectors used in these settings include oncolytic viruses, self-replicating RNA vectors, and non-replicative viral and non-viral vectors. The use of viral vectors, especially when they have replication capacity, provides an additional adjuvant effect that has been shown to enhance antitumor responses. This review covers the most recent studies involving the use of gene therapy vectors to deliver ICIs to gastrointestinal tumors.

show abstract

“…The positive-sense single-stranded RNA genome of alphaviruses ranges from 11 and 12 kb in length, with a cap structure at the 5′ end and a poly-A tail at the 3′ end. The genome consists of two open reading frames (ORFs); one is flanked by a 5′ cap and an untranslated region which encodes four nonstructural proteins, and the other which is controlled by the subgenomic promoter and encodes five structural proteins [ 4 , 5 ]. Having mRNA characteristics, the genome of alphaviruses initiates the viral replication process upon introduction to susceptible cells and, as a result, is known as infectious.…”

Section: Introductionmentioning

confidence: 99%

“…The human mortality rate post-infection with alphaviruses differs between New-World and Old-World alphaviruses. The mortality rate in Old-World alphaviruses, such as CHIKV, is very low (~0.03%), whereas the mortality rate in some New-World alphaviruses, such as EEEV, is 50–75% [ 5 ]. Although most alphaviruses cause acute human diseases, many patients suffer from chronic debilitating sequelae following infection with these viruses.…”

Section: Introductionmentioning

confidence: 99%

The Host Non-Coding RNA Response to Alphavirus Infection

Behnia

Bradfute

2023

Viruses

Self Cite

View full text Add to dashboard Cite

Alphaviruses are important human and animal pathogens that can cause a range of debilitating symptoms and are found worldwide. These include arthralgic diseases caused by Old-World viruses and encephalitis induced by infection with New-World alphaviruses. Non-coding RNAs do not encode for proteins, but can modulate cellular response pathways in a myriad of ways. There are several classes of non-coding RNAs, some more well-studied than others. Much research has focused on the mRNA response to infection against alphaviruses, but analysis of non-coding RNA responses has been more limited until recently. This review covers what is known regarding host cell non-coding RNA responses in alphavirus infections and highlights gaps in the knowledge that future research should address.

show abstract

The life cycle of the alphaviruses: From an antiviral perspective

Cited by 11 publications

References 289 publications

Chikungunya fever

Chikungunya fever

Local Delivery of Immunomodulatory Antibodies for Gastrointestinal Tumors

The Host Non-Coding RNA Response to Alphavirus Infection

Contact Info

Product

Resources

About