The Impact of African Swine Fever Virus
ASFV poses major risks to pig health and food security worldwide.
Juliette Dupré, Katarzyna Magdalena Dolata, Gang Pei, Aidin Molouki, Lynnette C Goatley, Richard Küchler, Timothy K Soh, Jens B Bosse, Aurore Fablet, Mireille Le Dimna, Grégory Karadjian, Edouard Hirchaud, Christopher L Netherton, Linda K Dixon, Ana Luisa Reis, Damien Vitour, Marie-Frédérique Le Potier, Axel Karger, Grégory Caignard
― 6 min read
Table of Contents
- How Does ASFV Spread?
- Why is ASFV a Big Deal?
- The Inner Workings of ASFV
- The Role of MGFs in ASFV
- Investigating ASFV Interactions
- The Sneaky Ways ASFV Manipulates the Immune Response
- The Dance of Proteins
- The Trials and Tribulations of ASFV Mutants
- Conclusion: The Ongoing Battle Against ASFV
- Original Source
- Reference Links
African Swine Fever Virus, commonly known as ASFV, is a big and enveloped virus that belongs to the Asfarviridae family. This virus causes African Swine Fever (ASF), a disease that only affects pigs (or more scientifically, suids). ASF is a serious concern for pig farmers and has been causing major troubles across the globe. Once a pig gets infected, the results can be catastrophic, leading to high mortality rates and significant economic losses in the pig farming industry.
How Does ASFV Spread?
ASFV has a few sneaky ways to spread. It can jump from one pig to another through direct contact, which is why keeping pigs in clean and separated areas is so critical. It can also hitch a ride on contaminated meat products, which means that leftovers from infected pigs could spread the virus if not disposed of properly. Even things like clothes or equipment that have come in contact with the virus can spread it, along with certain ticks known as Ornithodoros. These ticks are like pesky little party crashers in the pig world that can carry and transmit the virus.
Why is ASFV a Big Deal?
ASFV is a major player when it comes to threats to pig health and food security around the world. This virus is an unwanted guest that comes with no available vaccines or treatments. It's on the watchlist for the World Organisation for Animal Health (WOAH), which means it’s considered important enough to keep an eye on. The high death rate among domestic pigs makes ASFV a significant danger to farmers and creates a heavy economic burden for many countries.
The Inner Workings of ASFV
Now, diving a bit deeper, ASFV has a complex structure. Its genome, which holds all the instructions for making the virus, is made of double-stranded DNA and can range from 170 to 193 kilobases in size. If you think of the genome as a book, there’s a “core region” in the middle that is pretty stable, while the areas surrounding it have a lot of genetic variations. Interestingly, a substantial number of the genes in this virus don’t seem to have known functions, which is a bit puzzling for scientists.
When ASFV enters a pig's cells, it starts to make itself comfortable. It begins to express many viral gene products, which means it's producing parts of itself to take over the host's cellular functions. This can interfere with the normal processes in the pig's cells, causing havoc.
The Role of MGFs in ASFV
Within ASFV, there are specific gene families, including the Multigene Family (MGF) genes. These genes have developed through a process known as gene duplication and play various roles. There are five distinct MGFs, and they can influence how virulent (or deadly) the virus is. Some strains of ASFV that are less dangerous have been found to lack certain MGF genes. Researchers have even isolated a naturally attenuated strain known as OUR T1988/3, which lacks a handful of MGF genes.
Some studies suggest that these MGFs can determine the range of hosts a virus can infect. Furthermore, one of them, MGF360, has been shown to inhibit the immune response in pigs by messing with the production of Interferons, which are proteins the body uses to fight off infections. By doing this, ASFV can stay hidden from the pig's immune system and continue to reproduce, making itself a larger threat.
Investigating ASFV Interactions
To understand how ASFV operates, scientists have been trying to identify which proteins interact with ASFV proteins. They wanted to know how ASFV proteins might be taking over the pig cells. Using methods like affinity tag purification-mass spectrometry (AP-MS) and high-throughput yeast two-hybrid (HT-Y2H), researchers have been able to discover various cellular interactions.
One important protein that was discovered through these methods is BANF1, which stands for Barrier-to-Autointegration Factor 1. BANF1 plays a role in many cellular processes, such as maintaining the integrity of the genome and responding to DNA damage. Surprisingly, BANF1 was found to interact with ASFV proteins MGF360-21R and A151R, suggesting that ASFV might be using it to its advantage during infection.
The Sneaky Ways ASFV Manipulates the Immune Response
When ASFV infects a pig, it tries to hide from the immune system. Studies show that both MGF360-21R and A151R can interfere with the immune response, specifically by blocking the production of type I interferons. This is a critical aspect of the pig's defense mechanism against viruses.
When researchers silenced the BANF1 gene in infected pigs, they noted that ASFV replication decreased, meaning BANF1 might actually be helpful for the virus in some way. This suggests that understanding the interactions between ASFV proteins and host proteins could lead to new ways of fighting the virus.
The Dance of Proteins
To illustrate this, think of the interplay between ASFV proteins and the host proteins like a dance. The ASFV proteins, A151R and MGF360-21R, invite the host protein BANF1 to join in, and together, they create a complex that helps the virus avoid the immune system. They seem to have a choreographed performance that makes it hard for the host’s defenses to detect them.
When one of the viral proteins is removed (like in the GeorgiaΔA151R mutant), the dance gets disrupted, and the host’s immune system begins to recognize the virus, leading to increased production of interferons.
The Trials and Tribulations of ASFV Mutants
Researchers have created specific mutants of ASFV, such as GeorgiaΔA151R and GeorgiaΔMGF360-21R, to study their functions further. These mutants showed different growth patterns and responses in infected cells. They found that without A151R, ASFV had a tougher time replicating and was more recognizable by the pig's immune system.
In simple terms, it’s like a magician who needs specific props to perform their tricks. Without the right props (in this case, the right proteins), the magic show (or viral replication) just doesn’t go as planned.
Conclusion: The Ongoing Battle Against ASFV
ASFV is a complex and sneaky virus that poses a significant risk to the pig industry worldwide. The constant battle of wits between ASFV and the pig’s immune system tells a story of survival and adaptation. Researchers continue to investigate the myriad interactions between ASFV proteins and host cellular machinery to find new ways to combat this resilient virus.
As with any good story, the plot is still unfolding. With every discovery, scientists uncover more about how ASFV operates, offering hope for better prevention and control measures in the future. After all, when it comes to viruses, it’s a game of survival of the fittest – and right now, ASFV is playing to win.
So, let’s all keep our fingers crossed that we can come out on top in this ongoing battle, ensuring healthy pigs and safe food supplies across the globe!
Title: Exploring virus-host interactions through combined proteomic approaches identifies BANF1 as a new essential factor for African Swine Fever Virus.
Abstract: African swine fever virus (ASFV) causes a highly lethal disease in pigs and represents a significant threat to the global pork industry due to the lack of effective vaccines or treatments. Despite intensive research, many ASFV proteins remain uncharacterized. This study aimed to elucidate the functions of two ASFV proteins, MGF360-21R and A151R, through comprehensive analysis of their interactions with host proteins. Using affinity purification-mass spectrometry and yeast two-hybrid screening approaches, we identified the host protein barrier- to-autointegration factor 1 (BANF1) as a key interactor of both viral proteins. Biochemical and colocalization assays confirmed these interactions and demonstrated that MGF360-21R and A151R expression leads to cytoplasmic relocalization of BANF1. Functionally, BANF1 silencing significantly reduced ASFV replication, indicating its proviral role. Given BANF1s established function in regulating the cGAS/STING-dependent type I interferon (IFN-I) response, we postulated that A151R and MGF360-21R could inhibit this pathway. Using different strategies, we showed that both A151R and MGF360-21R did indeed inhibit IFN-I induction. Generation of ASFV deficient of A151R or MGF360-21R showed that both mutant viruses enhanced the host IFN response in primary porcine macrophages compared to wild-type virus. However, their capacity to inhibit this pathway could occur through mechanisms independent of BANF1. Proteomic analysis of BANF1 interactors during ASFV infection highlighted potentially roles in chromatin remodeling, nuclear transport, and innate immune response pathways. Altogether, our data provide new insights into ASFV-host interactions, identifying BANF1 as an important new host factor required for replication and uncovering novel functions for A151R and MGF360-21R. Author SummaryAfrican swine fever virus (ASFV) is a highly contagious and deadly disease affecting pigs worldwide, for which there are currently no effective vaccines or treatments. Despite extensive research, many ASFV proteins remain poorly understood. Our study investigated two ASFV proteins, MGF360-21R and A151R, to better understand their functions and interactions with host proteins. Using proteomic approaches, we found both these viral proteins interact with a host protein called barrier-to-autointegration factor 1 (BANF1). Importantly, BANF1 silencing significantly reduced ASFV replication, indicating its important role in the viral life cycle. We also showed that MGF360-21R and A151R help the virus evade the immune system by blocking the production of interferons, which are key defensive molecules against viral infections. However, this immune evasion does not seem to depend on their interaction with BANF1. Additionally, our analysis of BANF1s interactions during ASFV infection revealed potential roles in chromatin remodeling, nuclear transport, and the innate immune response. These findings provide new insights into how ASFV interacts with its host and highlight BANF1 as a critical factor in viral replication and immune evasion. Our work contributes to a better understanding of ASFV and could pave the way for developing more effective strategies to fight this virus.
Authors: Juliette Dupré, Katarzyna Magdalena Dolata, Gang Pei, Aidin Molouki, Lynnette C Goatley, Richard Küchler, Timothy K Soh, Jens B Bosse, Aurore Fablet, Mireille Le Dimna, Grégory Karadjian, Edouard Hirchaud, Christopher L Netherton, Linda K Dixon, Ana Luisa Reis, Damien Vitour, Marie-Frédérique Le Potier, Axel Karger, Grégory Caignard
Last Update: 2024-12-06 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.12.05.627126
Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.05.627126.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.