Mutation of the Theiler's virus leader protein zinc-finger domain impairs apoptotic activity in murine macrophages

Son, Kyung-No; Liang, Zhiting; Lipton, Howard L.

doi:10.1016/j.virusres.2013.09.001

Cited by 4 publications

(4 citation statements)

References 25 publications

(27 reference statements)

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“…Hato et al [17] demon strated that the L protein inhibited the type I IFN response by blocking IRF-3 dimerization and traffcking of IRF-3 from the cytoplasm to the nucleus. Mutating the L protein led to an impaired apoptotic activity in murine mac-rophages, suggesting that not only is the L protein important for apoptosis, but slight changes to the viral genome can have a signifcant effect on viral pathogenesis [20]. Although it has not yet been shown with SAFV, other rodent cardioviruses that have a close nucleotide sequence homology to SAFV, such as TMEV, have been shown to inhibit type I IFNs [21].…”

Section: Picornaviruses Suppress the Innate Immune Responsementioning

confidence: 99%

Picornavirus Infection Leading to Immunosuppression

2014

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Viruses, such as HIV, hepatitis A, poliovirus, coxsackievirus B3 and foot-and-mouth disease virus, use a variety of mechanisms to suppress the human immune system in order to evade clearance by the host. Therefore, investigating how a few changes in the viral genome of a nonlethal virus can lead to an alteration in disease, from survivable to immunosuppression and death, would provide valuable information into viral pathogenesis. In addition, we propose that gaining a better insight into how these viruses suppress an antiviral immune response could lead to viral-based therapeutics to combat specifc autoimmune diseases such as multiple sclerosis and Type 1 diabetes.

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Section: Picornaviruses Suppress the Innate Immune Responsementioning

confidence: 99%

Picornavirus Infection Leading to Immunosuppression

2014

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“…In other cases, viruses can infect and damage cells involved in phagocytosis, like macrophages, as seen in influenza virus and dengue virus infections (Egberink and Horzinek, 1992; VandeWoude and Apetrei, 2006). Similarly, PV can block the production of type I interferon (IFN), leading to T cell depletion, or can modulate immune cells apoptosis and autophagy mechanisms (Lei et al, 2011; Lee et al, 2012; Son et al, 2013). In bivalves, the primary role of haemocytes is pathogen killing and elimination through phagocytosis, encapsulation, production of cytotoxic molecules, antimicrobial peptides, and secretion of inflammatory cytokines (de la Ballina, 2022; Song et al, 2010; Cheng, 1981).…”

Section: Discussionmentioning

confidence: 99%

A WIDESPREAD PICORNAVIRUS AFFECTS THE HAEMOCYTES OF THE NOBLE PEN SHELL (PINNA NOBILIS) LEADING TO IMMUNOSUPPRESSION

Carella,

Prado,

Vico

et al. 2023

Preprint

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The widespread mass mortality of the noble pen shell (Pinna nobilis) has occurred in several Mediterranean countries in the past seven years. Single-stranded RNA virus affecting immune cells and leading to immune disfunction have been widely reported in human and animal species. Here we present data linkingP. nobilismass mortality events (MMEs) to haemocyte picornavirus (PV) infection. This study was performed on 30 specimens, from wild and captive populations. We sampledP. nobilisfrom two regions of Spain, Catalonia [24 animals] and Murcia [two animals]), and one region in Italy (Venice [four animals]). The low number of analyzed specimens was due to the scarcity of remaining individuals in the Mediterranean Sea. In 100% of our samples, ultrastructure revealed the presence of a virus (20nm diameter), capable of replicating within granulocytes and hyalinocytes, leading to the accumulation of complex vesicles of different dimensions within the cytoplasm. As the PV infection progressed, dead haemocytes, infectious exosomes, and budding of extracellular vesicles were visible, along with endocytic vesicles entering other cells. The THC (total haemocyte count) values observed in both captive (eight animals) (3.5 x 104- 1.60 x105ml-1cells) and wild animals (14 samples) (1.90 - 2.42 x105ml-1cells) were lower than those reported before MMEs. Sequencing ofP. nobilis(six animals) haemocyte cDNA libraries revealed the presence of two main sequences ofPicornavirales, familyMarnaviridae. The highest number of reads belonged to animals that exhibited active replication phases and abundant viral particles from Trasmission Electron Microscopy (TEM) observations. These sequences correspond to the genusSogarnavirus- a picornavirus identified in the marine diatomChaetoceros tenuissimus(namedC. tenuissimusRNA virus type II). Real time PCR performed on the two most abundant RNA viruses previously identified byin silicoanalysis revealed positive results only for the sequences similar toC. tenuissimusRNA virus. These results may not be considered conclusive of picornavirus identification in noble pen shell haemocytes, and require further studies. Our findings suggest that picornavirus infection likely causes immunosuppression, making individuals prone to opportunistic infections which is a potential cause for the MMEs observed in the Mediterranean.

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“…In other cases, viruses can infect, and damage cells involved in phagocytosis, such as macrophages, as seen in influenza virus and dengue virus infections ( 60 , 61 ). Similarly, PV can block the production of type I interferon (IFN), leading to T-cell depletion, or modulate immune cell apoptosis and autophagy mechanisms ( 62 – 64 ). In bivalves, the primary role of hemocytes is pathogen killing and elimination through phagocytosis, encapsulation, production of cytotoxic molecules and antimicrobial peptides, and secretion of inflammatory cytokines ( 65 – 68 ).…”

Section: Discussionmentioning

confidence: 99%

A widespread picornavirus affects the hemocytes of the noble pen shell (Pinna nobilis), leading to its immunosuppression

Carella,

Prado,

De Vico

et al. 2023

Front. Vet. Sci.

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IntroductionThe widespread mass mortality of the noble pen shell (Pinna nobilis) has occurred in several Mediterranean countries in the past 7 years. Single-stranded RNA viruses affecting immune cells and leading to immune dysfunction have been widely reported in human and animal species. Here, we present data linking P. nobilis mass mortality events (MMEs) to hemocyte picornavirus (PV) infection. This study was performed on specimens from wild and captive populations.MethodsWe sampled P. nobilis from two regions of Spain [Catalonia (24 animals) and Murcia (four animals)] and one region in Italy [Venice (6 animals)]. Each of them were analyzed using transmission electron microscopy (TEM) to describe the morphology and self-assembly of virions. Illumina sequencing coupled to qPCR was performed to describe the identified virus and part of its genome.Results and discussionIn 100% of our samples, ultrastructure revealed the presence of a virus (20 nm diameter) capable of replicating within granulocytes and hyalinocytes, leading to the accumulation of complex vesicles of different dimensions within the cytoplasm. As the PV infection progressed, dead hemocytes, infectious exosomes, and budding of extracellular vesicles were visible, along with endocytic vesicles entering other cells. The THC (total hemocyte count) values observed in both captive (eight animals) (3.5 × 104–1.60 × 105 ml−1 cells) and wild animals (14 samples) (1.90–2.42 × 105 ml−1 cells) were lower than those reported before MMEs. Sequencing of P. nobilis (six animals) hemocyte cDNA libraries revealed the presence of two main sequences of Picornavirales, family Marnaviridae. The highest number of reads belonged to animals that exhibited active replication phases and abundant viral particles from transmission electron microscopy (TEM) observations. These sequences correspond to the genus Sogarnavirus—a picornavirus identified in the marine diatom Chaetoceros tenuissimus (named C. tenuissimus RNA virus type II). Real-time PCR performed on the two most abundant RNA viruses previously identified by in silico analysis revealed positive results only for sequences similar to the C. tenuissimus RNA virus. These results may not conclusively identify picornavirus in noble pen shell hemocytes; therefore, further study is required. Our findings suggest that picornavirus infection likely causes immunosuppression, making individuals prone to opportunistic infections, which is a potential cause for the MMEs observed in the Mediterranean.

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Mutation of the Theiler's virus leader protein zinc-finger domain impairs apoptotic activity in murine macrophages

Cited by 4 publications

References 25 publications

Picornavirus Infection Leading to Immunosuppression

Picornavirus Infection Leading to Immunosuppression

A WIDESPREAD PICORNAVIRUS AFFECTS THE HAEMOCYTES OF THE NOBLE PEN SHELL (PINNA NOBILIS) LEADING TO IMMUNOSUPPRESSION

A widespread picornavirus affects the hemocytes of the noble pen shell (Pinna nobilis), leading to its immunosuppression

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