In 1994, this team received their first samples of shrimp affected by white spot disease (WSD).
WSD is a disease which affects most of the aquatic crustaceans. WSD can cause up to 100% mortality. Obviously, this can have a serious economic impact on cultured shrimps (Fig.1).
Although this team had not previously worked with crustaceans, and this team led by Dr. Chu-Fang Lo had successfully identified the causative viral agent, white spot syndrome virus (WSSV) (Fig. 2).
Fig.1
Fig.2
The virus has a double-stranded circular DNA genome of over 300 kbp. Over 90% of the WSSV ORFs show no significant similarity to other known proteins. It is a very unique virus.
WSSV also has a very broad host range, the virus replicates very rapidly in the host, it has lots of anti-host defense strategies, thus it is a disease that is very difficult to control.
Until now, this team has published 160 papers. These publications reflect scientific progression of this team, from initially studying the characteristics of WSD outbreaks in shrimp, through studies of the unique features of its pathogen to the under-studied field of shrimp defense mechanisms and virus-host interactions.
It is well documented that insights from this team’s basic research prompted improvements in biosecurity practices in shrimp hatcheries and farms. Their work on the causative pathogen, WSSV (white spot syndrome virus), also contributed to its being assigned to the new virus family Nimaviridae. These achievements illustrate both the depth and the width of the team’s scientific enquiries, as well as their continuing efforts to emphasize the importance of marine pathogens and highlight their unique characteristics in contrast to the viruses, bacteria and other organisms that inhabit the terrestrial environment.
WSD is a very tough disease for the shrimp host to deal with. In our previous studies, we have looked at some of the strategies the virus uses to overcome the host’s defense.
For example, host ROS –or reactive oxygen species- is one line of host defense against an invading pathogen. But with WSSV , the host ROS can be neutralized at initial stage of infection (Fig. 4).
Fig 4. WSSV uses the PI3K-Akt-mTOR-regulated Warburg effect to reduce the ROS produced by the host in response to WSSV infection , and thereby restoring the cell to a state of redox balance and allowing the virus to successfully replicate.
Another host defense is the Iron withholding defense mechanism. However, White Spot Syndrome Virus Protein (PK1) Defeats the Host Cell’s Iron Withholding Defense Mechanism by Interacting with Host Ferritin (Fig. 5)
Fig. 5. The cellular labile iron pool (LIP) consists of the chelatable and rapidly exchangeable forms of cell iron.In normal cells, the excess free iron can be sequestered by apoferritin to maintain the iron homeostasis.In our study, we found that WSSV PK1 blocks iron homeostasis in infected cells to ensure an excess of free ferrous ions that the virus can use.
We also found that Sometimes instead of just defeating the host defenses, the virus actually takes advantages of them. Some defense proteins (e.g. NFkB and STAT) can even be co-opted by the WSSV IE1 gene. (Fig.6)
Fig. 6. Normally in response to stress, the activated STAT will trigger the expression of host immune proteins. However, if the virus is present in the cell, then instead of immune proteins, the activated STAT will trigger the expression of WSSV IE1, and this in turn will lead to viral gene expression and viral replication.
WSSV also express a novel DNA mimic protein. This protein, ICP11, is very highly expressed at the late stage of infection and it leads to the death of the shrimp (Fig.7)
Fig. 7 ICP11 prevents histone from binding to DNA – and the result is a disrupted nucleosome
WSD is pretty serious problem. What can we do about it? You might think that to control WSD, all you need to do is monitor and survey for the presence of the virus, and then quarantine, or otherwise keep separate, the virus and its shrimp host. To some extent, this is indeed helpful. However, let us look at the history of this disease. This disease emerged quite recently , ~ 25 years ago in East Asia. Since then, despite our best efforts, it’s spread to become an almost global pandemic. During 2010 to 2012, WSSV caused severe mortalities in cultured penaeid shrimp in Saudi Arabia, Mozambique and Madagascar. It was suggested by Dr. Lightner’s group in 2013 that the WSSV epidemics in these 3 countries were from a common source, and that this source was possibly the environment. This is quite depressing; It suggests that we need to look beyond diagnosis and quarantine. Right now, this is an enormous challenge. if we can not easily control the disease, we can still ask a slightly different question : What can we do to help the host more successfully defend itself against WSSV? Production of WSD resistant shrimp is part of solutions.
In addition to their current work in host-virus interactions, their research now includes another new, fast-moving shrimp disease (Acute Hepatopancreatic Necrosis Disease; AHPND), which is caused by a pathogenic strain of the opportunistic marine bacterium Vibrio parahaemolyticus. Publishing their AHPND research in a high impact journal, they reported that a non-pathogenic version of this organism becomes virulent by acquiring a plasmid that expresses a deadly toxin. This team has been recognized internationally for their groundbreaking work in the basic science of shrimp diseases and their application of cutting edge disease control technology to shrimp aquaculture.
For their R & D work for the shrimp aquaculture industry, this team was awarded a very competitive MoST Grant for Excellence from 2014 to 2018. They used this grant to mobilize a multidisciplinary team of experts in life sciences, environmental engineering, green architecture, management sciences, and social sciences. Working at NCKU, this team has been engaged in developing technologies for a science-based sustainable shrimp aquaculture industry. Since 2018, this team has been funded by grants from the MoE Excellent Research Center’s Higher Education Sprout Project and the MoST Excellent Research Center. With this support, the team continues to pursue a shrimp breeding program, while simultaneously establishing a 3-hectare shrimp farm in Hualien, with high biosecurity and the ability to cope with extreme changes of the weather. With this work, which is designed to increase the shrimp survival rate and thus directly benefit the shrimp farming industry, this team aims to make a major contribution both to the scientific community and to the industrial sector.