First primate model of Zika virus infection allows scientists to study new treatments

Scientists report in Nature Communications that healthy, pregnant rhesus macaque monkeys can be infected with Zika, providing a means for studying the mechanisms of infection. Pregnant macaques have comparable fetal development to humans, and the scientists say the macaques provide a model for testing vaccines and treatments for the virus, which is associated with fetal microcephaly and Guillain-Barré syndrome in adults.

 

Dr. Peter Barry, Director, Center for Comparative Medicine; Professor, Department of Pathology and Laboratory Medicine; Core Scientist, California National Primate Research Center; University of California, Davis (webpage):

Expertise: Mechanisms of viral pathogenesis in nonhuman primates; congenital infection and fetal disease by cytomegalovirus in nonhuman primates; nonhuman primate models of human viral infections

“This paper is a seminal paper for ultimately understanding mechanisms of Zika virus pathogenesis and designing prevention and treatment strategies, such as vaccines and antiviral drugs.  This paper demonstrates for the first time that a clinically-derived sample of Zika virus replicates in rhesus macaques and disseminates to multiples compartments throughout the animal.  This paper should be viewed as a critical first step in animal modeling of Zika virus, and the authors have provided an experimental foundation with which subsequent studies can build upon.

“Successful infection should not be viewed as unexpected as the first isolation of Zika virus in 1947 was found in rhesus macaques in an area of Uganda called Zika.  This paper demonstrates that recovery of Zika virus from infected humans in French Polynesia has not lost the capacity to replicate in rhesus macaques.

“The results of this paper are highly relevant for human health. Since infection of macaques with Zika has been established, multiple vaccines can be efficiently and rigorously optimized prior to clinical trials in humans.  It is encouraging for vaccine development that a second round of Zika infection did not appear to result in any detectable viral RNA in plasma, urine, or saliva.  Presumably the animals developed anti-Zika immune responses that conferred protective immunity against Zika reinfection.

“It is important to emphasize that, according to the authors, this ‘proof of concept’ study was not designed to rigorously study critical issues of Zika virus pathogenesis, particularly Guillain-Barré syndrome and microcephaly.  None of the non-pregnant animals exhibited clinical signs of disease. Given the rare occurrence of Guillain-Barré syndrome in Zika-infected humans, this may be similarly rare in Zika-infected rhesus macaques.

“Rhesus macaques and humans share many common features because of their close evolutionary relationship. The similarities between humans and macaques are far greater than between humans and any other tractable animal model.  The two pregnancies described in the paper were ongoing at the manuscript submission, and subsequent analyses will determine whether the fetuses were infected and whether Zika symptoms were observed.”

 

Dr. Amelia Pinto, Assistant Professor, Department of Molecular Microbiology & Immunology, Saint Louis University (webpage):

Expertise: Understanding the immune response to arboviruses including West Nile, chikungunya, Zika, and dengue.

“This study in a nonhuman primate provides an important contribution to our understanding of the course of Zika virus infection in primates and demonstrates the development of a protective immune response following infection, which suggests that there is protection against reinfection with Zika virus. The online updates prior to this publication and since is in itself a major step forward in sharing research that should be a model for resource sharing going forward.

“Different from the small animal models currently used, the macaques are not immune compromised so the natural course of infection and immune response can be studied. The study shows that these animals can become infected and, like humans, they shed virus in both urine and saliva, suggesting that they could be used to study other routes of transmission.  The subtle symptoms in the male and non-pregnant female macaques mimic the mild symptoms seen in the majority of humans infected with Zika. The authors note that sedation of the animals does impact the ability to detect subtle changes in the animal’s health, making it difficult to interpret some of their findings.

“The infection of pregnant female macaques provides some of the most interesting data within this study. Particularly interesting is the continued detection of virus in the plasma of the pregnant females that is not seen in the non-pregnant females and male macaques and does appear to mimic at least one report of persistent infection during pregnancy in humans.

“This study is ongoing, so from the results reported in this paper we cannot yet say that macaques are going to be a good model for understanding the links between Zika infection during pregnancy and the increased risk for microcephaly. However, the continued detection of virus in the pregnant macaques, which is not seen in the absence of pregnancy, does establish the macaques as a very good model for understanding Zika virus infection during pregnancy.

“This study of the natural course of Zika infection in macaques does not provide us with any understanding of a possible link between Zika infection and Guillain Barré syndrome. Macaques are most likely not going to be a good model for studying the potential association between Zika and Guillain Barré because the incidence of Guillain Barré is very low as the majority of people exhibit unapparent to mild symptoms.  Because the incidence is low for Guillain Barré we are going to need more studies in tissue culture and small animals with larger sample sizes.”

 

Declared interests (see GENeS register of interests policy):

Dr. Peter Barry: Dr. Barry previously co-authored a paper with Dr. Sallie Permar, a co-author of the current study.

 

Reference:

‘A rhesus macaque model of Asian-lineage Zika virus infection’Nature Communications, published June 28th, 2016.

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