High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus

Abstract

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.

Mathematical modeling of within‐host Zika virus dynamics

“…Red, circles: RM ‐infected mid‐first trimester of pregnancy. Blue, triangles: RM ‐infected late‐second or early‐third trimester of pregnancy, (B) in plasma of RM after infection with a Puerto Rican strain of ZIKV ( PRVABC 59) via mosquito vector, data taken from Dudley et al., (C) in plasma of RM after intrarectal (red, circles) or intravaginal (blue, triangles) infection with 10 7 PFU of ArD 41525 ZIKV , data taken from Haddow et al . In all panels, the dashed line represents the reported experimental limit of detection of the assay.…”

“…Since the reproductive ratio, R 0 , is the number of secondary infections produced by one infected cell when target cells are not limiting, the model requires that p/δ virions are able to infect R 0 cells. Experimental estimates find that the ratio of RNA (virions) to PFU, that is, infectious particles, 54 In all panels, the dashed line represents the reported experimental limit of detection of the assay. When samples contained undetectable ZIKV they are shown at the limit of detection…”

Macaque monkeys in Zika virus research: 1947–present

“…To mimic vector-borne transmission, our initial studies, and those of other groups, infected macaques subcutaneously with doses ranging from 10 2 to 10 6 PFU [46, 47, 51, 53, 63]. Intravenous inoculation has also been successfully utilized to infect macaques [54] and researchers at University of California Davis (UC-Davis) and others are exploring the use of intravaginal and intrarectal transmission to model sexual transmission [71]. Finally, intra-amniotic administration of ZIKV has been used for direct in utero infection of fetuses (Koen Van Rompay, personal communication, April 24, 2017).…”

“…We are not aware of any ZIKV-associated GBS in macaques, though this is not surprising given the rarity of GBS in people. In addition to natural history studies, nonpregnant macaques have been used to model sexual transmission of ZIKV, study tropism and persistence of ZIKV, characterize clinical isolates of ZIKV, and test ZIKV vaccine platforms [47, 50, 54, 56, 71]. …”

Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon

“…Non-human primates (NHPs) are the best documented animal reservoirs for ZIKV (and related flaviviruses). ZIKV infection has been achieved in male, and non-pregnant and pregnant female rhesus (Macacca mulatta) (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) cynomolgus (Macacca fascicularis) (22,32) and pigtail macaques (Macacca nemestrina) (33) following subcutaneous (SC) inoculation with French Polynesian (H/PF/2013), (20) Puerto Rican (PRVABC59, 2015) (21,22,(30)(31)(32), Brazilian (Brazil/ZKV2015; Zika virus/H.sapiens-tc/BRA/2015/Brazil_SPH2015) (26)(27)(28)(29) and Cambodian strains of ZIKV (FSS13025) (32). There are now several reports of ZIKV infection in pregnant macaques, with one study describing infection of a single pigtail macaque using an Asian strain (FSS13025 strain; Cambodia, 2010) (33), and four studies with pregnant rhesus macaques infected with either the French Polynesian or Puerto Rican strains (20,23,30,31).…”