African swine fever virus: current state and future perspectives in vaccine and antiviral research.

Abstract (Expand)

African swine fever (ASF) is among the most significant of swine diseases for which no effective vaccines and antivirals are available. The disease, which is endemic in Africa, was introduced to … Trans-Caucasian countries and the Russian Federation in 2007, where it remains prevalent today among domestic pigs and wild boars. Although some measures were implemented, ASF continues to pose a global risk for all countries, and thereby highlighting the importance of vaccine and antiviral research. In this review, an overview of research efforts toward the development of effective vaccines during the past decades is presented. As an alternative to vaccine development, the current state in antiviral research against ASFV is also presented. Finally, future perspectives in vaccine and antiviral research giving emphasis on some strategies that may allow researchers to develop effective countermeasures against ASF are discussed.

Authors: Hovakim Zakaryan, Yolanda Revilla

Date Published: 15th Mar 2016

Publication Type: Journal

A study of lymphoid organs and serum proinflammatory cytokines in pigs infected with African swine fever virus genotype II.

Abstract (Expand)

African swine fever virus (ASFV), the causative agent of one of the most important viral diseases of domestic pigs for which no vaccine is available, causes immune system disorders in infected animals. … In this study, the serum levels of proinflammatory cytokines, as well as the histological and cellular constitution of lymphoid organs of pigs infected with ASFV genotype II were investigated. The results showed a high degree of lymphocyte depletion in the lymphoid organs, particularly in the spleen and lymph nodes, where ASFV infection led to a twofold decrease in the number of lymphocytes on the final day of infection. Additionally, ASFV-infected pigs had atypical forms of lymphocytes found in all lymphoid organs. In contrast to lymphocytes, the number of immature immune cells, particularly myelocytes, increased dramatically and reached a maximum on day 7 postinfection. The serum levels of TNF-α, IL-1β, IL-6, and IL-8 were evaluated. Proinflammatory cytokines showed increased levels after ASFV infection, with peak values at 7 days postinfection, and this highlights their role in the pathogenesis of ASFV. In conclusion, this study showed that ASFV genotype II, like other highly virulent strains, causes severe pathological changes in the immune system of pigs.

Authors: Hovakim Zakaryan, Victorya Cholakyans, Lusine Simonyan, Alla Misakyan, Elena Karalova, Andranik Chavushyan, Zaven Karalyan

Date Published: 24th Mar 2015

Publication Type: Journal

Pathology of porcine peripheral white blood cells during infection with African swine fever virus.

Abstract (Expand)

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF) that is the significant disease of domestic pigs. Several studies showed that ASFV can influence on porcine blood … cells in vitro. Thus, we asked ourselves whether ASFV infection results in changes in porcine blood cells in vivo. A series of experiments were performed in order to investigate the effects of ASFV infection on porcine peripheral white blood cells. Nine pigs were inoculated by intramuscular injection with 10⁴ 50% hemadsorbing doses of virus (genotype II) distributed in Armenia and Georgia. The total number of fifteen cell types was calculated during experimental infection.

Authors: Zaven Karalyan, Hovakim Zakaryan, Hranush Arzumanyan, Khachik Sargsyan, Henrik Voskanyan, Lina Hakobyan, Liana Abroyan, Aida Avetisyan, Elena Karalova

Date Published: 28th Feb 2012

Publication Type: Journal

Interferon status and white blood cells during infection with African swine fever virus in vivo.

Abstract (Expand)

African swine fever virus (ASFV) is the causative agent of African swine fever that is the significant disease of domestic pigs, with high rates of mortality. ASFV is double-stranded DNA virus whose … genes encode some proteins that are implicated in the suppression of host immune response. In this study, we have modeled in vivo infection of ASFV for determination of interferon (IFN) status in infected pigs. We measured the level of IFN-α, -β and -γ by enzyme-linked immunosorbent assay and showed that the level of IFN-α sharply decreased during infection. Unlike IFN-α, the level of IFN-β and -γ increased from the 2nd and 4th days post-infection, respectively. Also, we analyzed the population dynamics of peripheral white blood cells of infected pigs due to their important role in host immune system. We showed that the atypical lymphocytes appeared after short time of infection and this result is in accordance with our previous study done in vitro. At the last day of infection about 50% of the total white blood cells were destroyed, and the remaining cells were represented mainly by small-sized lymphocytes, reactive lymphocytes and lymphoblasts.

Authors: Z Karalyan, H Zakaryan, Kh Sargsyan, H Voskanyan, H Arzumanyan, H Avagyan, E Karalova

Date Published: 15th Jan 2012

Publication Type: Journal

Phenotypic and cytologic studies of lymphoid cells and monocytes in primary culture of porcine bone marrow during infection of African swine fever virus.

Abstract (Expand)

We have modeled in vitro infection of African swine fever virus (ASFV) in primary unstimulated cells of the porcine bone marrow and have studied the phenotypical changes in the population of porcine … lymphoid cells by cytophotometry. Monocytes and large-sized lymphocytes completely vanished in 72 h of infection which is result of high sensitivity of those cells to ASFV. We describe DNA synthesis in monocytes at 24 h post infection. Cytophotometry of the uninfected cells revealed the few number of atypical lymphocytes and lymphoblasts after 72 h of cultivation; whereas in viral infected cultures, atypical cells appeared in large quantity (about 14%) with 24 h. Most of atypical lymphocytes and lymphoblasts had altered nucleus, and only a small number of atypical cells had additional nucleus. The cytophotometry of main and additional nuclei showed that DNA content didn't exceed diploid standard which indicates that the additional nuclei were consequence of fragmentation of nuclei in lymphocytes.

Authors: E M Karalova, Kh V Sargsyan, G K Hampikian, H E Voskanyan, L O Abroyan, A S Avetisyan, L A Hakobyan, H H Arzumanyan, H S Zakaryan, Zaven A Karalyan

Date Published: 24th Dec 2010

Publication Type: Journal

Antiviral screening of natural, anti-inflammatory compound library against African swine fever virus.

Abstract (Expand)

African swine fever virus (ASFV) is a major threat to pig production and the lack of effective vaccines underscores the need to develop robust antiviral countermeasures. Pathologically, a significant … elevation in pro-inflammatory cytokine production is associated with ASFV infection in pigs and there is high interest in identifying dual-acting natural compounds that exhibit antiviral and anti-inflammatory activities.

Authors: Joshua A Jackman, Astghik Hakobyan, Rafayela Grigoryan, Roza Izmailyan, Charles C Elrod, Hovakim Zakaryan

Date Published: 25th Apr 2024

Publication Type: Journal

Glycerol Monolaurate Inhibits Wild-Type African Swine Fever Virus Infection in Porcine Macrophages.

Abstract (Expand)

Naturally abundant antimicrobial lipids, such as fatty acids and monoglycerides, that disrupt membrane-enveloped viruses are promising mitigants to inhibit African swine fever virus (ASFV). Among … mitigant candidates in this class, glycerol monolaurate (GML) has demonstrated particularly high antiviral activity against laboratory-adapted ASFV strains. However, there is an outstanding need to further determine the effects of GML on wild-type ASFV strains, which can have different virulence levels and sensitivities to membrane-disrupting compounds as compared to laboratory-adapted strains. Herein, we investigated the antiviral effects of GML on a highly virulent strain of a wild-type ASFV isolate (Armenia/07) in an in vitro porcine macrophage model. GML treatment caused a concentration-dependent reduction in viral infectivity, and there was a sharp transition between inactive and active GML concentrations. Low GML concentrations had negligible effect on viral infectivity, whereas sufficiently high GML concentrations caused a >99% decrease in viral infectivity. The concentration onset of antiviral activity matched the critical micelle concentration (CMC) value of GML, reinforcing that GML micelles play a critical role in enabling anti-ASFV activity. These findings validate that GML can potently inhibit wild-type ASFV infection of porcine macrophages and support a biophysical explanation to guide antimicrobial lipid performance optimization for pathogen mitigation applications.

Authors: Joshua A Jackman, Erik Arabyan, Hovakim Zakaryan, Charles C Elrod

Date Published: 25th Sep 2023

Publication Type: Journal

Antiviral activity of brequinar against African swine fever virus infection in vitro.

Abstract (Expand)

African swine fever virus (ASFV) is a double-stranded DNA virus that causes an acute and hemorrhagic disease in domestic swine, resulting in significant economic losses to the global porcine industry. … The lack of vaccines and antiviral drugs highlights the urgent need for antiviral studies against ASFV. Here, we report that brequinar (BQR), which is a specific inhibitor of dihydroorotate dehydrogenase, robustly inhibits ASFV replication in Vero cells, as well as in porcine macrophages. We demonstrate that BQR exerts its antiviral activity in a dose-dependent manner through the depletion of pyrimidine pool. Although BQR does not affect the synthesis of an early viral protein, pI215L, the synthesis of late viral proteins, p17 and p72, is suppressed in the presence of BQR. We also show that BQR is able to induce cellular antiviral response in ASFV-infected macrophages by enhancing the expression of interferon-stimulated genes. Taken together, our study reveals that targeting nucleotide biosynthesis represents a promising strategy for developing antiviral agents against ASFV.

Authors: Rafayela Grigoryan, Erik Arabyan, Roza Izmailyan, Zaven Karalyan, Nuno Jordão, Fernando Ferreira, Hovakim Zakaryan

Date Published: 23rd May 2022

Publication Type: Journal

Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus.

Abstract (Expand)

Naturally occurring plant flavonoids are a promising class of antiviral agents to inhibit African swine fever virus (ASFV), which causes highly fatal disease in pigs and is a major threat to the swine … industry. Currently known flavonoids with anti-ASFV activity demonstrate a wide range of antiviral mechanisms, which motivates exploration of new antiviral candidates within this class. The objective of this study was to determine whether other flavonoids may significantly inhibit ASFV infection <i>in vitro</i>. We performed a cell-based library screen of 90 flavonoids. Our screening method allowed us to track the development of virus-induced cytopathic effect by MTT in the presence of tested flavonoids. This screening method was shown to be robust for hit identification, with an average Z-factor of 0.683. We identified nine compounds that inhibit ASFV Ba71V strain in Vero cells. Among them, kaempferol was the most potent and exhibited dose-dependent inhibition, which occurred through a virostatic effect. Time-of-addition studies revealed that kaempferol acts on the entry and post-entry stages of the ASFV replication cycle and impairs viral protein and DNA synthesis. It was further identified that kaempferol induces autophagy in ASFV-infected Vero cells, which is related to its antiviral activity and could be partially abrogated by the addition of an autophagy inhibitor. Kaempferol also exhibited dose-dependent inhibition of a highly virulent ASFV Arm/07 isolate in porcine macrophages. Together, these findings support that kaempferol is a promising anti-ASFV agent and has a distinct antiviral mechanism compared to other anti-ASFV flavonoids.

Authors: Erik Arabyan, Astghik Hakobyan, Tamara Hakobyan, Rafaella Grigoryan, Roza Izmailyan, Aida Avetisyan, Zaven Karalyan, Joshua A Jackman, Fernando Ferreira, Charles C Elrod, Hovakim Zakaryan

Date Published: 21st Oct 2021

Publication Type: Journal

A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity.

Abstract (Expand)

African swine fever virus (ASFV) is the causal agent of a fatal disease of domestic swine for which no effective antiviral drugs are available. Recently, it has been shown that microtubule-targeting … agents hamper the infection cycle of different viruses. In this study, we conducted in silico screening against the colchicine binding site (CBS) of tubulin and found three new compounds with anti-ASFV activity. The most promising antiviral compound (6b) reduced ASFV replication in a dose-dependent manner (IC50 = 19.5 μM) with no cellular (CC50 &gt; 500 μM) and animal toxicity (up to 100 mg/kg). Results also revealed that compound 6b interfered with ASFV attachment, internalization and egress, with time-of-addition assays, showing that compound 6b has higher antiviral effects when added within 2-8 h post-infection. This compound significantly inhibited viral DNA replication and disrupted viral protein synthesis. Experiments with ASFV-infected porcine macrophages disclosed that antiviral effects of the compound 6b were similar to its effects in Vero cells. Tubulin polymerization assay and confocal microscopy demonstrated that compound 6b promoted tubulin polymerization, acting as a microtubule-stabilizing, rather than a destabilizing agent in cells. In conclusion, this work emphasizes the idea that microtubules can be targets for drug development against ASFV.

Authors: Samvel Sirakanyan, Erik Arabyan, Astghik Hakobyan, Tamara Hakobyan, Garri Chilingaryan, Harutyun Sahakyan, Arsen Sargsyan, Grigor Arakelov, Karen Nazaryan, Roza Izmailyan, Liana Abroyan, Zaven Karalyan, Elina Arakelova, Elmira Hakobyan, Anush Hovakimyan, Andre Serobian, Marco Neves, João Ferreira, Fernando Ferreira, Hovakim Zakaryan

Date Published: No date defined

Publication Type: Journal

Inhibition of African swine fever virus in liquid and feed by medium-chain fatty acids and glycerol monolaurate.

Abstract (Expand)

The ongoing African swine fever virus (ASFv) epidemic has had a major impact on pig production globally and biosecurity efforts to curb ASFv infectivity and transmission are a high priority. It has … been recently identified that feed and feed ingredients, along with drinking water, can serve as transmission vehicles and might facilitate transboundary spread of ASFv. Thus, it is important to test the antiviral activity of regulatory compatible, antiviral feed additives that might inhibit ASFv infectivity in feed. One promising group of feed additive candidates includes medium-chain fatty acids (MCFA) and monoglyceride derivatives, which are known to disrupt the lipid membrane surrounding certain enveloped viruses and bacteria.

Authors: Joshua A Jackman, Astghik Hakobyan, Hovakim Zakaryan, Charles C Elrod

Date Published: 8th Dec 2020

Publication Type: Journal

Antiviral agents against African swine fever virus.

Abstract (Expand)

African swine fever virus (ASFV) is a significant transboundary virus that continues to spread outside Africa in Europe and most recently to China, Vietnam and Cambodia. Pigs infected with highly … virulent ASFV develop a hemorrhagic fever like illness with high lethality reaching up to 100%. There are no vaccines or antiviral drugs available for the prevention or treatment of ASFV infections. We here review molecules that have been reported to inhibit ASFV replication, either as direct-acting antivirals or host-targeting drugs as well as those that act via a yet unknown mechanism. Prospects for future antiviral research against ASFV are also discussed.

Authors: Erik Arabyan, Armen Kotsynyan, Astghik Hakobyan, Hovakim Zakaryan

Date Published: 17th Jul 2019

Publication Type: Journal

Evidence of hemolysis in pigs infected with highly virulent African swine fever virus.

Abstract

The research was conducted to understand more profoundly the pathogenetic aspects of the acute form of the African swine fever (ASF).

Authors: Zaven Karalyan, Hovakim Zakaryan, Elina Arakelova, Violeta Aivazyan, Marina Tatoyan, Armen Kotsinyan, Roza Izmailyan, Elena Karalova

Date Published: 14th Dec 2016

Publication Type: Journal

Powered by
 (v.1.15.0-main)
About ArmLifeBank | Funding and Programmes | Credits
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH