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(Winnie Lin / The McGill Tribune)

McGill researchers develop new model for Zika virus experiments

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The spread of new and emerging viruses poses a constant threat to public health and presents a concern to developing and developed countries alike. Population growth, climate change, and the increasing ease and speed of travel have exacerbated the transmission of these viruses.

Overpopulation results in the construction of homes in previously unsettled areas, providing zoonotic viruses—viruses that normally infect animals—with the opportunity to transmit to humans. The original case of the most recent Ebola outbreak was a two-year-old boy in a newly-built village in Guinea who came into contact with fruit bats, the natural reservoir for the virus.

Rising global temperatures are giving mosquito-borne diseases, such as malaria and yellow fever, chances to infect naïve populations, which were previously protected from these diseases by cold temperatures.

The Zika virus (ZIKV), a previously mild infection endemic to central Africa and Southeast Asia in the late 20th century, spread with the aid of modern travel and mutated to cause fetal microcephaly. Microcephaly is the name of the condition where infants are born with an abnormally small head.

Among recent emerging viruses, ZIKV is especially insidious as pregnant women who become infected exhibit mild and nonspecific symptoms, which often cause the infection to go undetected.

There are currently no drugs or vaccines for ZIKV, and treatments are usually aimed at alleviating symptoms. Additionally, the first diagnosis of a Zika infection often stems from the tragic realization that a newborn is afflicted with microcephaly, which poses significant developmental and behavioural consequences.

A number of challenges exist to produce an effective ZIKV vaccine, the chief of which is a lack of a suitable model to conduct experiments on the virus. Another difficulty is the virtual absence of any previous scientific knowledge on ZIKV. Before the epidemic in South America, the virus did not cause any severe symptoms and was thus not labelled as a top candidate to secure research funding.   

Recent research conducted by Dr. Martin Richer and Dr. Selena Segan, assistant professors in the Department of Microbiology and Immunology, could be a critical step in producing a suitable mouse model system for ZIKV study. The paper, published Feb. 23 in PLOS Pathogens, outlined a procedure to analyze ZIKV infections in mice with fully functional immune systems.

Previous studies have focused primarily on immunocompromised mice, since researchers were interested in the mechanism that caused the disease. However, the development of a vaccine against infectious pathogens requires intimate knowledge of how a host responds to infection. Not only did the paper outline an immunocompetent mouse model for ZIKV, it also characterized T cells—a type of white blood cell—as they responded to the virus.

In particular, the group discovered a conserved region of ZIKV’s envelope protein that these T cells respond to, called an epitope. It is conserved in 103 of the 104 published ZIKV gene sequences. The paper states that this finding could be an important step in the development of a vaccine against Zika.

However, virtually all currently approved vaccines use antibodies to generate protection. Antibodies are produced by B cells—another subtype of white blood cells—and the epitopes they respond to are often not the same as those of T cells.

“It’s very difficult to create a T cell-mediated vaccine, mostly because we don’t yet know that much about them,” Richer said in an interview with The McGill Tribune. “We need more basic research into cell types, such as cytotoxic CD8 T cells.”

Cytotoxic CD8 T cells are white blood cells involved in the killing of infected cells and are one of the cell types analyzed in their publication.

There is certainly a long road ahead for the creation of a ZIKV vaccine, but the development of an immunocompetent mouse model is a major step in this process. The analysis of B cell and antibody responses, as well as the discovery of new epitopes in different mouse strains, and whether the same epitopes can be found in humans, remain open and exciting avenues for further investigation.

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