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Zika hides out in body’s hard-to-reach spots

In rhesus monkeys, virus detected in cerebrospinal fluid, lymph nodes long after infection

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12:00pm, April 27, 2017
Zika virus

HIDE AND SEEK  Zika virus (red) remains in the central nervous system much longer than it does in the bloodstream, which could help explain its effects on the brain.

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Zika virus plays hard to get.  

Weeks after the virus disappears from the bloodstream, it still lingers in the lymph nodes and the central nervous system of rhesus monkeys, researchers report online April 27 in Cell. That could help explain why Zika infection can cause neurological problems in both infants and adults.

“Zika does stick around for a lot longer than we originally thought,” says Dan Streblow, a virologist at Oregon Health & Science University in Portland who wasn’t involved in the study. Streblow’s lab recently reported in PLOS Pathogens that Zika can also linger in rhesus monkeys’ reproductive tracts and peripheral nervous systems. And recent studies in humans have shown evidence of the virus hanging around in semen (SN Online: 2/14/17). Now, it appears the central nervous system and lymph nodes are also long-term hiding places.

That persistence could help explain why Zika “does substantial damage in the central nervous system,” says Dan Barouch, a study coauthor and virologist at Harvard Medical School. Infection in utero can cause microcephaly in infants, for instance, and the virus has been linked to an increased risk for a neurological autoimmune disease called Guillain-Barré syndrome in adults (SN: 4/2/16, p. 29).

Barouch and colleagues infected rhesus monkeys with Zika and monitored the early stages of infection. The virus disappeared from the monkeys’ bloodstreams after 10 days. But it lingered for as long as 42 days in cerebrospinal fluid, which circulates throughout the brain, and up to 72 days in the lymph nodes. Even though antibodies that recognize and disable the Zika virus appeared within days in the bloodstream, they weren’t detected in the cerebrospinal fluid during the study.

A look at how the monkeys were making certain proteins revealed a few potential reasons for the virus’s persistence. Monkeys with ongoing Zika infection in their cerebrospinal fluid made more of a protein called mTOR and a set of other proteins that interact with mTOR, the researchers found. That makes sense because mTOR, also called mechanistic target of rapamycin, has previously been shown to influence both immune response and neural development, Barouch says. Increased levels of the protein might be contributing to Zika’s effects on the brain, though more research is needed to show exactly how.

Sick monkeys also made less of certain proteins that coordinate communication between cells. Blocking those cell-to-cell messages might prevent immune cells from making their way to the virus’s hiding places. That group of proteins is similarly affected by dengue virus, suggesting that the two illnesses might share some of the same infection tricks.

The findings suggest that the virus might have neurological effects beyond what’s been seen so far, Barouch says. And it adds another layer of complexity for scientists searching for a treatment: A successful treatment will need to remove the virus from the bloodstream as well as the nooks and crannies in the body where it seems to hide.

It also makes finding a preventative strategy more important than ever. Barouch’s lab is one of many working on a Zika vaccine to stop infection from ever setting in (SN: 3/18/17, p. 12). Their vaccine is currently in early stage clinical trials.

Citations

M. Aid et al. Zika virus persistence in the central nervous system and lymph nodes of rhesus monkeys. Cell. Published online April 27, 2017. doi:10.1016/j.cell.2017.04.008.

A. Hirsch et al. Zika virus infection of rhesus macaques leads to viral persistence in multiple tissues. PLOS Pathogens. March 9, 2017. doi: 10.1371/journal.ppat.1006219.

Further Reading

M. Rosen. DNA may offer rapid road to Zika vaccine. Science News, Vol. 191, March 18, 2017, p. 12.

M. Rosen. See how long Zika lasts in semen and other bodily fluids. Science News Online, February 14, 2017.

L. Sanders and M. Rosen. Scientists probe Zika’s link to neurological disorder. Science News, Vol. 189, April 2, 2016, p. 29.

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