Intranasal infection and contact transmission of Zika virus in guinea pigs

Abstract

Zika virus (ZIKV) is primarily transmitted to humans through mosquito bites or sexual contact. The excretion and persistence of contagious ZIKV in various body fluids have been well documented in ZIKV patients; however, the risk of direct contact exposure remains unclear. Here, we show that guinea pigs are susceptible to ZIKV infection via subcutaneous inoculation route; infected guinea pigs exhibit seroconversion and significant viral secretion in sera, saliva, and tears. Notably, ZIKV is efficiently transmitted from infected guinea pigs to naïve co-caged animals. In particular, intranasal inoculation of ZIKV is fully capable of establishing infection in guinea pigs, and viral antigens are detected in multiple tissues including brain and parotid glands. Cynomolgus macaques also efficiently acquire ZIKV infection via intranasal and intragastric inoculation routes. These collective results from animal models highlight the risk of exposure to ZIKV contaminants and raise the possibility of close contact transmission of ZIKV in humans.

Zika virus infection in Collaborative Cross mice

“…However, the explosive growth of ZIKV research since 2015 has spurred the development of new animal models, revealing pathogenic mechanisms and providing systems for evaluating therapeutic interventions. The most significant models of ZIKV infection are non-human primates and mice (7), but ZIKV disease also has been studied in guinea pigs, hamsters, tree shrews, and swine (27-35). Mice offer significant advantages in terms of cost, scale, speed, and genetic tractability, enabling mechanistic studies that are not feasible in non-human primate models.…”

Animal Models of Zika Virus Sexual Transmission

“…Several other animal models have been used to study ZIKV but most are not focused on sexual transmission. These models include guinea pigs [109][110][111], hamsters [112], bats [113], chick embryos, piglets [114,115] and boars [116]. Porcine fetuses were shown to present mild to severe neuropathology upon ZIKV infection [114,115].…”

“…One study with ZIKV challenge mid-gestation showed no evidence of infection [109]; however, Kumar et al show guinea pigs inoculated subcutaneously with PRVABC59 had viremia and presented signs such as fever, hunched posture and detectable viral RNA in the blood [110]. Deng et al showed that intranasally-infected guinea pigs have virus in the sera, saliva and tears [111].…”

Comparative models for human nasal infections and immunity

“…Guinea pigs have also been intranasally infected with ZIKA virus (ZIKAV). Nasal infection with ZIKAV results in infection of the brain, parotid glands, tears, saliva and sera but NALT immune responses were not evaluated (Deng et al, 2017). Of interest, nasal vaccination of guinea pigs with a genital herpesvirus HSV2 vaccine results in protection to genital herpes and elicits systemic specific IgG but not IgA titers (Persson et al, 2016).…”

“…After 7 days post inoculation, IgM and IgA antibodies were detected, followed by IgG. Thus, a strong infection in the nasal mucosa was established in A129 mice (Deng et al, 2017). A vaccine against the envelope protein E of ZIKAV was tested in this mouse strain and production of neutralizing antibodies was able to confer protection against ZIKAV and other Flaviviridae (Sumathy et al, 2017).…”