Assessing Zika virus replication and the development of Zika-specific antibodies after a mid-gestation viral challenge in guinea pigs

Abstract

Primary Zika virus (ZIKV) infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development.

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].…”

“…The guinea pig models report conflicting results. 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].…”

Zika virus-based immunotherapy enhances long-term survival of rodents with brain tumors through upregulation of memory T-cells

“…ZIKV H/PF/2013 (passage 4) was obtained from the European Virus Archive (001v-EVA1545) and cultured using previously established protocols [11]. ZIKV was passaged on Vero cells to generate working stocks of virus which were then concentrated by the ultracentrifugation of virus-containing media over a sucrose cushion, as described previously [12]. Multiple working ZIKV stocks were made from the same parent stock.…”

Research Models and Tools for the Identification of Antivirals and Therapeutics against Zika Virus Infection

“…In addition to subcutaneous infection, other infection routes including intranasal infection and contact transmission of Zika virus could be demonstrated using the guinea pig model, highlighting its suitability to study transmission pathways [ 227 ]. However, not all clinical aspects can be reproduced, as circulating ZIKV strains seemed not to be pathogenic during the pregnancy of immunocompetent guinea pigs and did not interfere with offspring development [ 228 ]. Nevertheless, in contrast to other small animal models, the guinea pig model is physiologically and immunologically more similar to humans [ 229 ].…”