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. 2017 Oct 6;11(10):e0005990.
doi: 10.1371/journal.pntd.0005990. eCollection 2017 Oct.

Pathogenesis and sexual transmission of Spondweni and Zika viruses

Erin M McDonald  1 , Nisha K Duggal  1 , Aaron C Brault  1
Affiliations

Pathogenesis and sexual transmission of Spondweni and Zika viruses

Erin M McDonald et al. PLoS Negl Trop Dis. .

Abstract

The Spondweni serogroup of viruses (Flaviviridae, Flavivirus) is comprised of Spondweni virus (SPONV) and Zika virus (ZIKV), which are mosquito-borne viruses capable of eliciting human disease. Numerous cases of ZIKV sexual transmission in humans have been documented following the emergence of the Asian genotype in the Americas. The African ZIKV genotype virus was previously implicated in the first reported case of ZIKV sexual transmission. Reports of SPONV infection in humans have been associated with non-specific febrile illness, but no association with sexual transmission has been reported. In order to assess the relative efficiency of sexual transmission of different ZIKV strains and the potential capacity of SPONV to be sexually transmitted, viral loads in the male reproductive tract and in seminal fluids were assessed in interferon α/β and -γ receptor deficient (AG129) mice. Male mice were inoculated subcutaneously with Asian genotype ZIKV strains PRVABC59 (Puerto Rico, 2015), FSS13025 (Cambodia, 2010), or P6-740 (Malaysia, 1966); African genotype ZIKV strain DakAr41524 (Senegal, 1984); or SPONV strain SAAr94 (South Africa, 1955). Infectious virus was detected in 60-72% of ejaculates collected from AG129 mice inoculated with ZIKV strains. In contrast, only 4% of ejaculates from SPONV-inoculated AG129 males were found to contain infectious virus, despite viral titers in the testes that were comparable to those of ZIKV-inoculated mice. Based on these results, future studies should be undertaken to assess the role of viral genetic determinants and host tropism that dictate the differential sexual transmission potential of ZIKV and SPONV.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Pathogenesis and viremia of ZIKV and SPONV in male AG129 mice.
Mice were inoculated s.c. with 3 log10 PFU of ZIKV strains PRVABC59, P6-740, FSS13025, DakAr41524 (n = 8 per virus strain), or SPONV strain SA Ar94 (n = 4), or inoculated i.p. with SPONV strain SA Ar94 at two doses, either 5.4 log10 PFU or 3 log10 PFU (n = 8 each). (A) Survival curve for mice inoculated with the ZIKV strains. DakAr41524 vs. any other ZIKV strain (p<0.05); PRVABC59 vs. any other ZIKV strain (p<0.05). (B) Survival curve for mice inoculated with the SPONV strain. SA Ar94 vs. DakAr41524 and PRVABC59 (p<0.001). (C) Weight of mice inoculated with the ZIKV strains, shown as a percentage of initial weight. (D) Weight of mice inoculated with the SPONV strain, shown as a percentage of initial weight. (E) Mean viremia of mice inoculated with ZIKV strains. Dpi 5 and 7: P6-740 and DakAr41524 vs. PRVABC59 and FSS13025 (*, p<0.05). (F) Mean viremia of mice inoculated with the SPONV strain. Dpi 3: SA Ar94 vs. any ZIKV strain (p<0.05); dpi 5 and 7: SA Ar94 vs. DakAr41524 and P6-740 (p<0.01). Error bars represent standard deviations from the mean.
Fig 2
Fig 2. Tissue tropism of ZIKV and SPONV in male AG129 mice.
Mice were inoculated s.c. with ZIKV (n = 8 per virus strain) or inoculated i.p. with a SPONV strain at two doses (n = 8 each) or s.c. (n = 4). The i.p. and s.c. groups for SPONV were combined into a single group for analyses. (A) Viral titers in the testes. PRVABC59 vs. any other strain (p<0.001). (B) Viral titers in the epididymis. PRVABC59 vs. DakAr41524 and P6-740 (p<0.01); SA Ar94 vs. DakAr41524 (p<0.01). (C) Viral titers in the seminal vesicles. PRVABC59 vs. any other ZIKV strain (p<0.05); DakAr41524 vs. any other strain (p<0.05). (D) Viral titers in the brain. PRVABC59 vs. FSS13025, DakAr41524, and SA Ar94 (p<0.05) (E) Viral titers in the eye. SA Ar94 vs. P6-740 (p<0.05). (F) Testicular weight as a percentage of total body weight. Control vs. PRVABC59 (p<0.01).
Fig 3
Fig 3. Sexual transmission potential of ZIKV and SPONV in male AG129 mice.
(A) Viral titers in seminal fluids collected from mice inoculated with ZIKV strains. (B) Viral titers in seminal fluids collected from mice inoculated with SPONV strain SA Ar94. (C) Viral RNA copy in seminal fluids collected from mice inoculated with SPONV strain SA Ar94.
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