Rhesus Monkey Study Exposes Zika’s Hiding Places
Article May 18, 2017 | By Ruairi Mackenzie BSc
A new study has shed light on the disease activity of the Zika virus, which swept to global prominence in 2016 after infecting over 100,000 people in Brazil and spreading to 70 other countries. The research suggests Zika can use sanctuaries within the body to evade destruction by the immune system and that alteration of an important host cell pathway by the virus may underlie some of the virus’s debilitating disease outcomes.
According to the World Health Organization, Zika’s symptoms are “usually mild” and are not considered to be a major health concern. However, infection in pregnant women is linked to severe microcephaly and a variety of other birth defects in the gestating foetus. But, the mechanisms leading to these neurological outcomes are poorly understood.
Read more: Zika immunity molecule found
Researchers led by Dan Barouch at the Beth Israel Deaconess Medical Center and Harvard Medical School used rhesus monkey models to study how Zika moves around peripheral circulation and into the central nervous system (CNS). Rhesus monkeys are an excellent model for Zika, and show the same foetal disease and clinical phenotypes that are seen in humans.
The team measured how Zika spreads through a host’s body by measuring viral particle load. In the animals’ circulating plasma the virus was removed by innate and adaptive immunity after just 10 days. When viral loads were measured in other tissues such as in lymph nodes or the CNS’s cerebrospinal fluid (CSF), persistence was seen for up to 72 days.
Prof Barouch said “Our manuscript shows that Zika virus infection in monkeys can result in persistence of the virus in the central nervous system and lymph nodes for a prolonged period of time after virus is cleared in the blood. If such findings are also observed in humans, then there may be more CNS and lymphoid disease in Zika-infected humans than previously recognized.”
Related: monkeys protected by Zika DNA vaccine
The infected monkeys’ immune responses to the virus were also quantified. Zika-specific antibodies were found in circulating plasma. However, no such antibodies were detected in the CSF, despite a persistently high viral load. This suggests that Zika can hide undercover in body tissues and fluids where normal immune responses cannot reach.
Further experiments looked at which cellular signalling pathways correlate with Zika infection - these included the mTOR (Mechanistic target of rapamycin) pathway. mTOR has responsibility for controlling important cell processes such as autophagy and protein synthesis. The authors speculate that increased mTOR signalling could be due to the virus directly stimulating the pathway to boost survival of infected cells.
In their discussion, the authors noted that mTOR has been shown to cause microcephaly when overstimulated in transgenic neonatal mice and may explain some of the neurological damage Zika can cause.
Prof Barouch said “We speculate that viral persistence in the CNS as well as activation of transcriptomic pathways associated with neurologic defects (such as the mTOR pathway) may be related to the pathogenesis of the virus in the CNS, although that remains to be proven.”
Aid, Malika, Peter Abbink, Rafael A. Larocca, Michael Boyd, Ramya Nityanandam, Ovini Nanayakkara, Amanda J. Martinot et al. "Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys." Cell 2017.
Chronic pain is a multifaceted disorder that causes profound disability worldwide. It has long been known that psychological stress contributes to adverse chronic pain outcomes in patients, but it is unclear how this is initiated or amplified by stress. Now, researchers have published results showing that activation of microglia in the mouse spinal cord is responsible for increased pain sensitivity in response to stress.READ MORE
Thanks to advances in therapeutics, chronic myeloid leukemia has been transformed from a deadly cancer into a manageable, chronic condition. However, patients have to stay on these drugs their whole lives, as there isn't a diagnostic test sensitive enough to detect traces of the disease that threaten a relapse. This article delves into the unmet need for such a test, and explains why droplet digital PCR (ddPCR) is a strong candidate that may fill this gap.READ MORE
16th International Conference on Structural Biology
Mar 11 - Mar 12, 2019
10th International Tissue Repair and Regeneration Congress
Jun 13 - Jun 14, 2019
2nd International Conference on Pharmaceutical Research & Innovations in Pharma Industry
May 30 - May 31, 2019