[109]

[109]. carried out by scientists, because of the great prospects and value of anti-CSFV strategies in the prevention and control of CSF. Additionally, studies on anti-CSFV strategies could be used as a reference for other viruses in the Flaviviridae family, such as hepatitis C virus, dengue virus, and Zika virus. In this review, we aim to summarize the research on anti-CSFV strategies. In detail, host proteins affecting CSFV replication, drug candidates with anti-CSFV effects, and RNA interference (RNAi) targeting CSFV viral genes were mentioned and the possible mechanisms related to anti-CSFV effects were also summarized. genus within the Flaviviridae family. CSFV is an enveloped, single-stranded, positive-sense RNA virus containing a 12.3 kb RNA genome, which consists of a 5-untranslated region (5-UTR), a single large open reading frame (ORF), and a 3-UTR. A polypeptide precursor could be encoded by ORF of CSFV and then cleaved into four structural proteins (C, Erns, E1, and E2) and eight non-structural proteins (Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) through the processing of the polypeptide precursor by viral and cellular proteases (Figure 1) [1,3,4]. Open in a separate window Figure 1 Schematic description of virion structure and genome organization of classical swine fever virus (CSFV) [4]. This figure comes from the literature reported by Beer et al. [4] with some modifications. CSFV is an enveloped, single-stranded, positive-sense RNA virus. Glycoproteins (Erns, E1, and E2) are located on the external part of viral particles and are important for viral infection. CSFV RNA genome consists of a single large open reading frame (ORF) flanked by a 5-untranslated region (5-UTR) and a 3-UTR. A polypeptide precursor could be encoded by ORF of CSFV and then cleaved into four structural proteins (C, Erns, E1, and E2) and eight non-structural proteins (Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). Based on partial sequences of CSFV 5-UTR, E2, and NS5B, phylogenic typing of CSFV isolates worldwide was carried out. In general, CSFV strains could be classified into three genotypes (1, 2, and 3) and eleven subgenotypes (1.1C1.4, 2.1C2.3, and 3.1C3.4) [5,6]; subgenotype 2.1 isolates were DC661 further divided into three sub-subgenotypes (2.1aC2.1c) [7,8,9]. Because of the high genetic diversity of subgenotype 2.1 strains, Gong et al. [10] suggested dividing the subgenotype 2.1 strains into ten sub-subgenotypes (2.1aC2.1j). As reported, CSFV strains of genotype 1, 2, and 3 are all epidemic in the world, while strains of genotype 2 have gradually become dominant globally [11,12,13,14]. CSFV strains DC661 virulence, ranging from high, moderate, to low virulence, is the crucial determinant of CSFV pathogenicity in pigs. CSFV infection can lead to an acute, subacute, chronic, or asymptomatic disease in pigs depending on CSFV strains virulence and other factors, such as the hosts age and immune status [15]. Although CSFV strains with different virulence exist globally, more and more reports show that the currently circulating strains are mainly moderately virulent [16,17,18,19]. Currently, the World Organization for Animal Health (OIE) lists 38 CSF-free members, which mainly locate in North America, part of South America, Oceania, and a large part of the European Union. CSF is still endemic in Asia, South and Central America, Eastern Europe, and parts of Africa. Additionally, specific zones in Brazil, Colombia, and Ecuador are declared CSF-free by OIE, while the other zones in these countries remain CSF-endemic [20]. Additionally, there is a risk of CSF re-emergence in CSF-free areas due to the existence of CSF-endemic regions in the world, as well as the reservoir of CSFV in wild boars. For instance, in 2018, CSF re-emerged in Japan after 26 years of CSF-free status, affecting both domestic pigs and wild boars [12]. Thus, as an endemic and re-emerging virus in pigs, CSFV is still a threat to the worlds pig industry. Biosecurity measures are crucial for preventing and controlling CSF. According to the guidance of OIE, strict sanitary prophylaxis is the first barrier to prevent CSF outbreaks [21]. In brief, some key points could be employed, such as maintaining effective communication between veterinary authorities, veterinary practitioners, and pig farmers, establishing a reliable disease reporting system, implementing strict quarantine, and enhancing hygiene measures to prevent contact between domestic pigs and wild boars [21]. Laboratory diagnostic techniques are also needed. Rapid and sensitive detection methods for CSFV infection, such as reverse transcription-polymerase chain reaction (RT-PCR) [22], SYBR Green or TaqMan real-time RT-PCR [23,24], and reverse transcription loop-mediated isothermal amplification (RT-LAMP) [25], are crucial to informing the appropriate control measures. Additionally, due to that wild boars.Additionally, in recent years, novel subunit marker vaccines based on the CSFV E2 protein have been developed for alternative options against CSF [26]. drug candidates with DC661 anti-CSFV effects, and RNA interference (RNAi) targeting CSFV viral genes were mentioned and the possible mechanisms related to anti-CSFV effects were also summarized. genus within the Flaviviridae family. CSFV is an enveloped, single-stranded, positive-sense RNA virus containing a 12.3 kb RNA genome, which consists of a 5-untranslated region (5-UTR), a single large open reading frame (ORF), and a 3-UTR. A polypeptide precursor could be encoded by ORF of CSFV and then cleaved into four structural proteins (C, Erns, E1, and E2) and eight non-structural proteins (Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) through the processing of the polypeptide precursor by viral and cellular proteases (Figure 1) [1,3,4]. Open in a separate window Figure 1 Schematic description of virion structure and genome organization of classical swine fever virus (CSFV) [4]. This figure comes from the literature reported by Beer et al. [4] with some modifications. CSFV is an enveloped, single-stranded, positive-sense RNA virus. Glycoproteins (Erns, E1, and E2) are located on the external part of viral particles and are important for viral infection. CSFV RNA genome consists of a single large open reading frame (ORF) flanked by a 5-untranslated region (5-UTR) and a 3-UTR. A polypeptide precursor could be encoded by ORF of CSFV and then cleaved into four structural proteins (C, Erns, E1, and E2) and eight non-structural proteins (Npro, p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B). Based on partial sequences of CSFV 5-UTR, E2, and NS5B, phylogenic typing of CSFV isolates worldwide was carried out. In general, CSFV strains could be classified into three genotypes (1, 2, and 3) and eleven subgenotypes (1.1C1.4, 2.1C2.3, and 3.1C3.4) [5,6]; subgenotype 2.1 isolates were further divided into three sub-subgenotypes (2.1aC2.1c) [7,8,9]. Because of the high genetic diversity of subgenotype 2.1 strains, Gong et al. [10] suggested dividing the subgenotype 2.1 strains into ten sub-subgenotypes (2.1aC2.1j). As reported, CSFV strains of genotype 1, 2, and 3 are all epidemic in the world, while strains of genotype 2 have gradually become dominant globally [11,12,13,14]. CSFV strains virulence, ranging from high, moderate, to low virulence, is the crucial determinant of CSFV pathogenicity in pigs. CSFV infection can lead to an acute, subacute, chronic, or asymptomatic disease in pigs depending on CSFV strains virulence and other factors, such as the hosts age and immune position [15]. Although CSFV strains with different virulence can be found globally, increasingly more reviews show which the presently circulating strains are generally reasonably virulent [16,17,18,19]. Presently, the World Company for Animal Wellness (OIE) lists 38 CSF-free associates, which generally locate in THE UNITED STATES, element of SOUTH USA, Oceania, and a big area Rabbit polyclonal to SMAD3 of the EU. CSF continues to be endemic in Asia, South and Central America, Eastern European countries, and elements of Africa. Additionally, particular areas in Brazil, Colombia, and Ecuador are announced CSF-free by OIE, as the various other areas in these countries stay CSF-endemic [20]. Additionally, there’s a threat of CSF re-emergence in CSF-free areas because of the life of CSF-endemic locations in the globe, aswell as the tank of CSFV in outrageous boars. For example, in 2018, CSF re-emerged in Japan after 26 many years of CSF-free position, affecting both local pigs and outrageous boars [12]. Hence, as an endemic and re-emerging trojan in pigs, CSFV continues to be a threat towards the worlds pig sector. Biosecurity measures are necessary for stopping and managing CSF. Based on the assistance of OIE, rigorous sanitary prophylaxis may be the initial barrier to avoid CSF outbreaks [21]. In short, some tips could be utilized, such as for example maintaining effective conversation between veterinary specialists, veterinary professionals, and pig farmers, building a trusted disease reporting program, implementing rigorous quarantine, and improving hygiene measures to avoid contact between local pigs and outrageous boars [21]. Lab diagnostic techniques may also be needed. Fast and sensitive recognition options for CSFV an infection, such as for example reverse transcription-polymerase string response (RT-PCR) [22], SYBR Green or TaqMan real-time RT-PCR [23,24], and invert transcription loop-mediated isothermal amplification (RT-LAMP) [25], are necessary to informing the correct control methods. Additionally, because of that outrageous boars are vunerable to CSFV, eradication of CSF from outrageous boars is.