ZIKV infection via mucosal challenges

ZIKV infection via mucosal challenges mmohns  2016-09-13
Given that Zika virus RNA is present in saliva of infected people and monkeys, we sought to determine if Zika virus could be transmitted by contact with saliva.

First, to assess whether or not mucosal infection was even possible, we challenged two animals (ZIKV-007 and ZIKV-010) with a high dose (10e6 PFU) of the Asian lineage virus via tonsillar challenge. In both challenges, we observed a 1-2 day delay of infection, followed by peak viremia around 5-6 days post infection. Viremia resolved to below the limit of detection by 14dpi similar to what we’ve seen in previous Zika challenges.

These experiments suggest that Zika infection is theoretically possible to transmit via a mucosal route given a high enough titer.

*gray lines represent historical viral loads of Zika infection in rhesus macaques

To follow these experiments, we subcutaneously challenged two animals (ZIKV-008 and ZIKV-011) with 10e4 PFU of the Asian lineage virus to use as a saliva donor for mucosal challenges in 5 other animals (ZIKV-009 and ZIKV-012).

The subcutaneously challenged animals displayed a viral trajectory consistent with previous Zika challenges.

Oral swabs from the ZIKV-008 donor animal were eluted in saline to use for saliva challenges in three additional animals (ZIKV-009), with saliva applied to either the tonsils, conjunctiva, or intranasal mucosa. The highest titer of ZIKV RNA isolated from oral swabs was just over 2,000 copies/ml.

A very low level blip was detected 2dpi in the ZIKV-009 animal that received donor saliva to the tonsils. However, a retest of this timepoint was negative for viral RNA. Additionally, none of the animals seroconverted (PRNT data pending later timepoints).

Alternatively, saliva was obtained via drool in the ZIKV-011 donor animal. This saliva/drool was used to directly infect the tonsillar mucosa of two animals (ZIKV-012). The highest titer of ZIKV RNA isolated from saliva/drool was just over 10,000 copies/ml.

ZIKV RNA was undetectable in both of the ZIKV-012 recipients and the animals did not seroconvert.

It is likely that the saliva viral loads in the donor animals was not nearly sufficient to infect the recipients.

While the theoretical transmission via a mucosal route is a possibility, it is likely that certain conditions need to be met, including high titer of virus in body fluids.