Item 43/100: Zika Virus
Holly Asbury, BS, Senior Biologist
ATCC® VR-84™ – Zika virus
First isolated in 1947 from a rhesus monkey in the Zika forest of Uganda and later from Aedes africanus mosquitoes, Zika virus (ZIKV) has since risen to global public prominence in the past two decades. Following its initial isolation, ZIKV could be detected in mosquito and human isolates in Africa and Southeast Asia. Due to increasing globalization and the spread of the Aedes mosquito disease vector, major outbreaks have occurred in Micronesia in 2007,1 in French Polynesia in 2013-2014, and in the Americas in 2015-2016, especially in Brazil, Puerto Rico, and the US Virgin Islands. Typically, disease caused by Zika virus infection is mild (e.g., fever or rashes) and approximately 80% of people infected experience no symptoms.2 However, in rare cases, as unfortunately happened in the 2015-2016 outbreak, complications can lead to Guillain-Barré syndrome, encephalopathy, and other neurological disorders.3,4 As the Aedes mosquitoes continue to spread farther north with the warming climate, they bring ZIKV and other arboviruses along with them, underscoring the importance of understanding these viruses and developing preventative measures and treatments. ATCC has in its collection the original 1947 ZIKV isolate, as well as 7 other strains of the virus including the 2015 Puerto Rican strain, PRVABC59.
Item 44/100: Mosquito-borne Dengue Virus and Public Health
Meghan Sikes, MS, Senior Biologist
ATCC® VR-1856™ – Dengue virus type 1
It may sometimes feel impossible to prevent pesky mosquito bites during the summertime or when on a tropical vacation; however, with the increased spread of mosquito-borne diseases, preventing these bites is essential. Based on the 2024 Lancet report on health and climate change, hotter weather and changes in precipitation will most likely favor increased transmission of mosquito-borne pathogens like dengue virus (DENV). In fact, dengue infections have drastically increased over the past twenty years, driven by climate changes and urbanization.5 Continued research and infection surveillance on the four serotypes of dengue virus will remain critical to address the global health burden this virus presents.
Dengue virus is of the genus Flavivirus and is transmitted via vector, primarily Aedes mosquitos, which are present in the Americas, Africa, Asia, and Europe.6 According to the Centers for Disease Control and Prevention, almost 4 billion people globally live in an area where there is a risk of contracting dengue.7 Symptoms of dengue can range from mild dengue to fatal shock,8 so it’s important to prevent infection by avoiding mosquito bites by using insect repellent and wearing long-sleeved shirts and pants. ATCC’s catalogue features Dengue virus serotypes 1-4, synthetic RNA for all serotypes, and a variety of anti-Dengue monoclonal antibodies. These products are useful in the growing field of mosquito-borne disease control, animal model development for DENV, and vaccine research.
Item 45/100: West Nile Virus
Baisali Ray, PhD, Senior Technical Writer
ATCC® VR-1510™ – West Nile virus
In 1999, infectious disease specialists in New York City were puzzled by the sudden cases of human encephalitis along with massive deaths of crows. Eventually, West Nile virus (WNV) was isolated from the brain tissue of the dead birds, marking the arrival of the virus in the western hemisphere, probably brought on by infected migratory birds or by the mosquito boom after extreme summer temperatures.9,10 Nowadays, WNV is commonly found in Africa, Europe, the Middle East, North America, and Australia and has the largest distribution worldwide among the arthropod-borne human pathogenic flaviviruses.11 WNV was first isolated in 1937 from the West Nile province in Uganda from a patient with fever.12 This strain (ATCC® VR 1510™) was deposited to ATCC by virologist Max Theiler, who won the Nobel Prize in 1951 for his work on the yellow fever vaccine. He was the only scientist to be awarded the Nobel prize for the development of a virus vaccine.
Birds, especially perching birds like the American robin, act as WNV reservoirs without demonstrating any clinical symptoms. Mosquito vectors (mostly Culex sp.) acquire the virus through a blood meal from infected birds. The virus is amplified and propagates to the salivary gland of the mosquito; it is then transmitted to either another bird or to a dead-end host like humans or horses. In humans, the resulting symptoms can range from mild fever to severe neurologic manifestations like flaccid paralysis or encephalitis. WNV strains of lineages 1 and 2 are the most virulent.13 Currently, there is no cure for WNV infection other than vector management. Since tampering with WNV reservoirs or vectors would lead to an imbalance in biodiversity and nature conservation, research for a safe and effective human vaccine is essential for preventing future outbreaks. ATCC has many different strains of WNV as well as genomic & synthetic RNA and anti-WNV monoclonal antibodies that can facilitate further research.
Item 46/100: Investigating Anaplasma marginale to Save the Cattle
Kenneth Montenegro, AS, Associate Biologist Intern (SPARC Program)
ATCC® VR-1436™ – Anaplasma marginale Theiler
To understand the underlying mechanisms of a disease, it is important to note the modes of transmission that facilitate its spread. Vector-borne diseases for example, require a separate entity to carry the pathogen to its next susceptible host. This applies to the tick-borne disease anaplasmosis, which is transmitted to humans, pets, and livestock by infected ticks. To control the spread of this disease, preventative measures like oral/topical tick & flea preventatives and the application of acaricides within buildings of agricultural settings have been used.14 Yet, this may not be enough as CDC reports have shown a rise in the average number of reported cases of anaplasmosis within 2000-2022 in the US.15
An affected area that may be overlooked by few is the spread of anaplasmosis in beef and dairy cattle farms and the associated economic impacts resulting from it. Bovine anaplasmosis, caused by the bacterial tick-borne pathogen Anaplasma marginale, can result in symptoms such as anemia and recurring parasitemic peaks, rendering the host prone to life-long infection.16 The pathogen was first discovered in 1910 by Sir Arnold Theiler when analyzing erythrocytes of South African cattle affected by the disease.17 Research examining the microbial agent today has included the use of A. marginale strain South Idaho, USA (S64-Id2AM) (ATCC® VR-1436™), which has proven useful in investigations involving camel anaplasmosis.18 ATCC’s tick-derived cell line ISE6 (ATCC® CRL-3576™) has also served as a beneficial model in studying tick-borne pathogens as it enables in vitro analysis of genera like Rickettsia, Anaplasma, and Ehrlichia.
The combination of preventative measures, treatment options, and ongoing research will help tackle the issue of tick-borne diseases. This will not only enhance public health but also mitigate the economic impacts associated with agricultural threats.
Item 47/100: Babesiosis: What is it and why is it spreading?
Sarah Robins, MS, Senior Biologist
ATCC® 30221™ – Babesia microti (Franca) Reichenow
Lyme disease, anaplasmosis, and ehrlichiosis—if you have a pet, you’ve probably heard these three tick-borne diseases mentioned at an annual vet visit or listed on the box of monthly flea and tick prevention. But have you heard of babesiosis? This tick-borne disease is caused by Babesia microti, a parasite that infects red blood cells and is the leading cause of babesiosis in the United States.19 Infection with this parasitic protozoan causes malaria-like illness with symptoms such as fever, chills, sweating, myalgias, fatigue, hepatosplenomegaly, and hemolytic anemia.20 While most B. microti infections are mild or asymptomatic in healthy individuals, the disease can be more severe or result in death for patients who are splenectomized, elderly, or immunocompromised.21 The severity of symptoms can be further exacerbated due to coinfection with other tick-borne diseases like Lyme disease.
Efforts to develop new therapies, understand the Babesia parasite's biology, and identify risk factors for the disease are ongoing. To support this important work, ATCC provides a variety of B. microti products, including strain Gray (ATCC® 30221™) and its genomic DNA (ATCC® 30221D™), and resources for other tick-borne diseases.
Item 48/100: The Ancient Parasitic Protozoan
Meghan Sikes, MS, Senior Biologist
ATCC® 30012™ – Leishmania major (Yakimoff and Schokhor) Bray et al.
Dating back to the 7th century BCE, lesions and sores resembling cutaneous leishmaniasis have been described; however, it wasn’t until the beginning of the 20th century that researchers tried to find the cause of these lesions. In 1900, William Boog Leishman discovered oval-shaped cells from a deceased soldier’s spleen sample. He hypothesized that these ovoid cells were degenerated forms of trypanosomes and that they caused an illness related to trypanosomiasis. Several years later, it was determined that these cells were a novel genus, which was named Leishmania after Leishman.22
Leishmania spp. are parasitic protozoa transmitted by the bite of infected female sandflies. These protozoa can cause three main clinical forms of leishmaniasis: cutaneous, mucosal, and visceral.23,24 Cutaneous leishmaniasis is the most common of these forms and is characterized by skin lesions that leave life-long scars; it is suspected to be caused by immune inflammatory signals and expression changes in specific genes.25,26
The World Health Organization estimates that one million new cases of leishmaniasis are diagnosed each year.27 However, despite affecting so many people globally, there is currently no vaccine and drug treatments are lacking for this neglected tropical disease. This is mainly due to the challenges associated with intracellular pathogens evading immune responses;28,29 once an intracellular parasite like Leishmania major gains access to the human body, it avoids our immune system response by hiding within our macrophages.
With various antigens that could be targeted, development of a leishmaniasis vaccine is a vast field with multiple vaccine candidates that have gone through preclinical and/or clinical trials. L. major (ATCC® 30012™) provides a great option for studying the development of live attenuated vaccines as it shows promise in stimulating Th1 immunity, which is responsible for pro-inflammatory responses against intracellular pathogens.30,31 Additionally, L. major can be used to identify novel leishmaniasis treatment options that target signal pathways or use bioactive compounds with anti-parasitic effects.32,33
Item 49/100: Oropouche Virus
Holly Asbury, BS, Senior Biologist
ATCC® VR-1228™ – Oropouche virus
The Oropouche virus (OROV) is an arthropod-borne virus transmitted primarily by the bite of infected biting midges (Culicoides paraensis).34 OROV was originally isolated in 1955 from a forest worker in Trinidad. In the 1960s, it emerged again in Brazil and has since remained endemic there in regions along the Amazon. Since 1989, OROV has been increasingly reported in additional nations in South and Central America and the Caribbean Islands. In 2024, more than 9,000 confirmed cases have been reported in Bolivia, Brazil, Colombia, Cuba, and Peru, but the prevalence of OROV infections is likely severely underestimated. Imported cases have also been reported in Spain, Italy, and Germany.35 The disease can cause fever, severe headache, chills, muscle aches, and joint pain, and can potentially progress to systemic infection affecting the nervous and blood systems. Vertical transmission of the infection from mother to unborn child is considered a significant concern as this causes congenital abnormalities like microcephaly.36 In 2024, the Pan American Health Organization (PAHO) issued a high-risk level epidemiological alert for OROV infection and emphasized the need strengthened surveillance and preventative measures.37 Thanks to the NIH/NIAID and CDC, ATCC has important OROV strains in its collection that can aid such important research and development: the original 1955 Trinidad isolate (ATCC® VR-1228™) and a 2024 isolate from the serum of patient in Italy with recent travel history to Cuba (ATCC® VR-3446™).
Item 50/100: Vaccine Development to Fight Chikungunya Virus
Chuck Na, MS, Innovation Manager
ATCC® VR-3360™ – Chikungunya virus
In the 1960s, doctors in Thailand were dealing with thousands of patients in the cities of Bangkok and Thonburi suffering from high fever, headache, rash, and severe joint and muscle pain.38 They found that the culprit was a recently identified virus: Chikungunya. It is a mosquito-transmitted virus with symptoms so severe that the name of the virus translates to “that which bends up,” referring to the bent posture in patients due to the severe pain in their joints.39 There was great concern that Chikungunya and other mosquito-transmitted viruses would quickly spread in highly populated areas. Outbreaks of Chikungunya have affected millions of people in Africa and Asia.40 Starting in the 1970’s, Connie Schmaljohn dedicated her career to studying hemorrhagic fever viruses. Spread by animals and person-to-person contact, these viruses damage the walls of blood vessels, causing blood leaks, and prevent normal blood clotting.41 Dr. Schmaljohn deposited an important tool at ATCC to study Chikungunya. The ATCC strain 181/clone 25 is an attenuated, or weakened, derivative of a Chikungunya virus that was originally isolated from a man in Thailand in 1962.40 Collaboratively developed by the University of Texas Galveston, the Centers for Disease Control, and others, the group published the results of generation of a live-attenuated viral vaccine strain in 2012. Scientists continue to use 181/25 as a vaccine control for better vaccine candidates; while 181/25 induces durable B-cell and antibody response, it elicits poor T cell responses which diminish at 1 year post vaccination.42
Thankfully, there is a new Chikungunya vaccine available. Approved in the US in 2023, IXCHIQ is a live attenuated vaccine derived from the LR2006-OPY1 strain, isolated from Reunion, a French island that is part of Mascarene in the Indian Ocean.43 As part of the validation of the IXCHIQ activity and published in 2024, researchers used 181/25 to represent the antibody capacity for the Asian genotype of Chikungunya.44 Chikungunya virus strain 181/25 (ATCC® VR-3360™) continues to be a powerful tool for studying Chikungunya vaccination. Thanks to the generous contribution by Dr. Connie Schmaljohn, recipient of many prestigious awards and currently the Director of the Integrated Research Facility for NIAID/NIH, researchers have access to this impactful tool to study Chikungunya immunity.
Item 51/100: Lyme Disease – 45 years later and no vaccine
Briana Benton, BS, Program Manager
ATCC® 35210™ – Borrelia burgdorferi Johnson et al. emend. Baranton et al.
Borrelia burgdorferi is a pathogenic spirochete bacterium responsible for causing Lyme disease. Lyme disease is a significant and growing health concern with confirmed case numbers consistently ranking in the top ten among all nationally notifiable conditions, and it is the most reported vector-borne disease in the United States.45,46 Lyme disease was first described in 1977 when there was a geographic clustering of children in Lyme, Connecticut, thought to have juvenile arthritis. In 1982, Dr. Willy Burgdorfer, after whom the bacterium was named, isolated spirochetes in the midgut tissues from ticks collected in a Lyme disease endemic area.47
B. burgdorferi is transmitted to humans through the bite of infected black-legged ticks and is characterized by its spiral shape and its ability to evade the immune system, making it particularly challenging to eradicate once it establishes an infection. Upon entering the human body, B. burgdorferi can spread to various tissues and organs, leading to a multisystemic infection. Early-stage symptoms include a characteristic bull's-eye rash, fever, malaise, headache, and joint pain. If left untreated, the bacterium can disseminate and cause more severe symptoms, such as neurological disorders, arthritic pain, and cardiac complications. Chronic Lyme disease can result in long-term health issues, severely impacting the quality of life. In 2016, it was estimated that the economic burden of reported Lyme disease cases in the US was somewhere between $345 to $968 million dollars per year.48
Given that the prevalence of Lyme disease has been steadily increasing, the need for an effective vaccine is paramount.49 The financial impact of Lyme disease is substantial, involving costs related to medical treatment, lost productivity, and long-term care. Developing and administering a vaccine would alleviate this economic burden by reducing the number of cases and, consequently, the associated healthcare costs. Efforts to develop a Lyme disease vaccine have been ongoing. The first vaccine, LYMERix, was introduced in the late 1990s but was discontinued by the manufacturer in 2002, citing insufficient consumer demand.50 Advancements in research have led to new vaccine candidates, showing promise in preventing infection. Valneva and Pfizer have developed a Lyme disease vaccine candidate, VLA15, that is currently in Phase 3 human trials. VLA15 is a multivalent, protein subunit vaccine that targets the outer surface protein A (OspA), the vaccine candidate covers the six most prevalent OspA serotypes expressed by the B. burgdorferi sensu lato species in North America and Europe.49,50 OspA is a surface protein expressed by the bacteria when present in a tick. Blocking OspA inhibits the bacterium’s ability to leave the tick and infect humans.51 Looking ahead, once there is an approved vaccine for the prevention of Lyme Disease, it will be equally important to ensure the vaccine is accessible and that the public is educated on the vaccine’s availability and effectiveness.
Did you know?
Vector-borne diseases account for more than 17% of all infectious diseases worldwide, causing more than 700,000 deaths annually. However, many are preventable through protective measures and community mobilization.52
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References
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LYMERix is a registered trademark of SmithKline Beecham Biologicals S.A. Pfizer is a registered trademark of Pfizer Inc. Valneva is a registered trademark of VALNEVA. IXCHIQ is a registered trademark of Valneva Austria GmbH.