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Nature Communications Jan 2024Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors...
Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virusĀ (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.
Topics: Animals; Humans; Alphavirus; Virus Internalization; Semliki forest virus; Alphavirus Infections; Culicidae
PubMed: 38245515
DOI: 10.1038/s41467-024-44872-5 -
Journal of Clinical Medicine Oct 2023The tick-borne encephalitis virus (TBEV) is the arboviral etiological agent of tick-borne encephalitis (TBE), considered to be one of the most important tick-borne viral... (Review)
Review
The tick-borne encephalitis virus (TBEV) is the arboviral etiological agent of tick-borne encephalitis (TBE), considered to be one of the most important tick-borne viral diseases in Europe and Asia. In recent years, an increase in the incidence of TBE as well as an increasing geographical range of the disease have been noted. Despite the COVID-19 pandemic and the imposition of restrictions that it necessitated, the incidence of TBE is rising in more than half of the European countries analyzed in recent studies. The virus is transmitted between ticks, animals, and humans. It seems that ticks and small mammals play a role in maintaining TBEV in nature. The disease can also affect dogs, horses, cattle, and small ruminants. Humans are incidental hosts, infected through the bite of an infected tick or by the alimentary route, through the consumption of unpasteurized milk or milk products from TBEV-infected animals. TBEV infections in humans may be asymptomatic, but the symptoms can range from mild flu-like to severe neurological. In Europe, cases of TBE are reported every year. While there is currently no effective treatment for TBE, immunization and protection against tick bites are critical in preventing this disease.
PubMed: 37892741
DOI: 10.3390/jcm12206603 -
Parasites & Vectors Oct 2023Culex (Barraudius) modestus (Ficalbi 1889) are found in temperate regions across Europe, Asia, and Northern Africa. These mosquitoes thrive during the summer and prefer... (Review)
Review
Culex (Barraudius) modestus (Ficalbi 1889) are found in temperate regions across Europe, Asia, and Northern Africa. These mosquitoes thrive during the summer and prefer to breed in permanent vegetative habitats such as rice paddies and marshes. Culex modestus feed on a wide range of bird species but are highly attracted to humans, which makes them a potential 'bridge' vector for enzootic pathogens. There is compelling evidence that Culex modestus is an efficient vector for West Nile virus, potentially capable of causing epidemics in humans and other mammals. This species is also a likely vector for Usutu virus, avian malaria (Plasmodium spp.), and parasitic heartworms (Dirofilaria spp.). Culex modestus can be morphologically identified at the larval and adult stages, and a distinctive phenotype of this species is their ability to overwinter. Despite the widespread establishment of this mosquito species and their role as vectors for human pathogens, we lack sufficient knowledge on this species to implement and evaluate targeted vector control measures. Since Culex modestus can be considered a potential public health threat, there is a need for a better understanding of this mosquito species.
Topics: Animals; Humans; Culex; Mosquito Vectors; Insect Vectors; Plant Breeding; Culicidae; West Nile virus; Mammals
PubMed: 37858198
DOI: 10.1186/s13071-023-05997-6 -
Virus Research Oct 2023Coronaviruses (CoVs) have been the source of multiple epidemics and a global pandemic since the start of century, and there is an urgent need to understand CoV biology... (Review)
Review
Coronaviruses (CoVs) have been the source of multiple epidemics and a global pandemic since the start of century, and there is an urgent need to understand CoV biology and develop better therapeutics. Here, we review the role of NSP16 in CoV replication, specifically its importance to 2'-O-methylation and CoV RNA capping. We describe the attenuation phenotypes of NSP16-mutant CoVs, the roles of MDA5 and IFITs in sensing and antagonizing viral RNA lacking 2'O methylation, and the dependence on 2'-O-methylation in other virus families. We also detail the growing body of research into targeting 2'-O-methylation for therapeutics or as a platform for live attenuated vaccines. Beyond its role in RNA capping, NSP16 may have yet uncharacterized importance to CoV replication, highlighting the need for continued studies into NSP16 functions. Understanding the full contribution of NSP16 to the replicative fitness of CoVs will better inform the development of treatments against future CoV outbreaks.
PubMed: 37634741
DOI: 10.1016/j.virusres.2023.199211 -
Pathogens (Basel, Switzerland) Jul 2023Aberrant adenosine diphosphate-ribose (ADP)-ribosylation of proteins and nucleic acids is associated with multiple disease processes such as infections and chronic... (Review)
Review
Aberrant adenosine diphosphate-ribose (ADP)-ribosylation of proteins and nucleic acids is associated with multiple disease processes such as infections and chronic inflammatory diseases. The poly(ADP-ribose) polymerase (PARP)/ADP-ribosyltransferase (ART) family members promote mono- or poly-ADP-ribosylation. Although evidence has linked PARPs/ARTs and macrophages in the context of chronic inflammation, the underlying mechanisms remain incompletely understood. This review provides an overview of literature focusing on the roles of PARP1/ARTD1, PARP7/ARTD14, PARP9/ARTD9, and PARP14/ARTD8 in macrophages. PARPs/ARTs regulate changes in macrophages during chronic inflammatory processes not only via catalytic modifications but also via non-catalytic mechanisms. Untangling complex mechanisms, by which PARPs/ARTs modulate macrophage phenotype, and providing molecular bases for the development of new therapeutics require the development and implementation of innovative technologies.
PubMed: 37513811
DOI: 10.3390/pathogens12070964 -
Frontiers in Cellular and Infection... 2023Dengue is prevalent in tropical and subtropical regions. As an arbovirus disease, it is mainly transmitted by and . According to the previous studies, temperature is... (Review)
Review
Dengue is prevalent in tropical and subtropical regions. As an arbovirus disease, it is mainly transmitted by and . According to the previous studies, temperature is closely related to the survival of mosquitoes, the proliferation of dengue virus (DENV) and the vector competence of to transmit DENV. This review describes the correlations between temperature and dengue epidemics, and explores the potential reasons including the distribution and development of mosquitoes, the structure of DENV, and the vector competence of mosquitoes. In addition, the immune and metabolic mechanism are discussed on how temperature affects the vector competence of mosquitoes to transmit DENV.
Topics: Animals; Aedes; Dengue Virus; Temperature; Mosquito Vectors; Dengue
PubMed: 37808907
DOI: 10.3389/fcimb.2023.1242173 -
Cureus Jul 2023The recent emergence and re-emergence of viral infections transmitted by vectors, Zika, chikungunya, dengue, and others, is a cause for international concern. Here, we... (Review)
Review
The recent emergence and re-emergence of viral infections transmitted by vectors, Zika, chikungunya, dengue, and others, is a cause for international concern. Here, we provide a summary of the current understanding of the transmission, clinical features, diagnosis, global burden, and the likelihood of future epidemics by these viruses. Arboviruses transmitted by mosquitoes are challenging to diagnose and can have surprising clinical complications. Dengue, chikungunya, and Zika are the most important diseases caused by arboviruses worldwide, especially in tropical and subtropical regions. These are transmitted to humans by day-biting and mosquitoes. In India, the increase in the incidence of dengue and chikungunya cases is primarily linked to the dissemination of . A rapid and accurate diagnosis is paramount for effectively controlling dengue outbreaks. As there is no vaccination or specific treatment available for these viruses, vector control is the only comprehensive solution available.
PubMed: 37575782
DOI: 10.7759/cureus.41717