Table 1.
Frequently used animal models for ZIKV infection and disease.
| Model organism | Advantages | Disadvantages | |
|---|---|---|---|
| IMMUNOCOMPROMISED MICE | |||
| IFN signaling deficient-mice | IFNI knock out (IFNAR1−/−; A129) | • Small animal model (size, generation time, handling, cost, etc.) • Large body of literature, availability of tools and reagents |
• Evolutionary distance • Immunodeficient |
| IFNI and II knock out (AG129) | • Replicates high viremia, dissemination to multiple organs, ataxia, tremor and paralysis • Study pathogenesis of eye disease |
• Replicate only some aspects of ZIKV infection | |
| C57BL/6 or BALB/c treated with anti-IFNAR1 mAb | • Study pathogenesis and persistence in male reproductive tract • Lethal and non-lethal models available |
• Lethality is age-dependent–100% mortality only in very young mice (3–4 weeks-old) | |
| IMMUNOCOMPETENT MICE | |||
| Neonate C57BL/6 or BALB/c | • Small animal model (size, generation time, handling, cost, etc.) • Large body of literature, availability of tools and reagents • Key brain development processes occur post-natally • Replicate pathologies of central nervous system • Sub-lethal—study long-term sequelae on survivors |
• Evolutionary distance • Replicate only some aspects of ZIKV infection |
|
| IMMUNOCOMPETENT PRIMATES | |||
| NHP | Rhesus macaques | • Evolutionary proximity—Similar physiology and immune response • Natural host |
• Large animal model (size, generation time, handling, cost, etc.) |
| Cynomolgus macaques | • Replicate viremia; spread to different organs and body fluids, changes in blood biochemistry and mostly elevated body temperature • Non-lethal |
• Ethical constraints of using primates in research | |
| INFECTION DURING PREGNANCY | |||
| Pregnant mice | IFNAR1−/− | • Small animal model (size, generation time, handling, cost, etc.) • Availability of tools and reagents • Replicates transplacental viral transmission |
• Evolutionary distance • Immunodeficient or not fully immunocompetent (SJL mice) |
| C57BL/6 treated with anti-IFNAR1 mAb | • Replicate pathological changes to brains of developing fetuses and intrauterine growth restrictions | ||
| Pregnant NHP | Rhesus macaques | • Evolutionary proximity—similar placental barrier and gestational development • Natural host |
• Large animal model (size, generation time, handling, cost, etc.) |
| Pigtail macaques | • Replicate persistent viremia and transplacental transmission | • Ethical constraints of using primates in research | |