Abstract

Background

Almost 115,000 people in the United States are currently on a transplant waitlist, which vastly exceeds the number of organ donors every year. This discrepancy emphasizes the need for retention of all possible donors. Those who have recently traveled to an area with an active outbreak of Zika virus (ZIKV) are often disqualified as a donor because immunosuppressed recipients would be at risk of a donor-derived ZIKV infection. Therefore, we define ZIKV tissue tropism and the risk of donor derived transmission.

Methods

We subcutaneously inoculated 15 Indian-origin rhesus macaques (RM) with a Puerto Rican isolate of ZIKV (PRVABC59). All RMs were inoculated in mid to early gestation.We inoculated during pregnancy because plasma viremia is typically prolonged in pregnancy and we wanted to model tissue tropism for donor derived transmission in the worst scenario of prolonged viremia. At 30, 65, and 105 days post-infection (dpi), the animals were euthanized and comprehensive necropsies were performed, which evaluated a minimum of 60 tissues per animal. ZIKV RNA was quantified in tissues via qRT-PCR.

Results

Plasma viremia duration was >10 days in 13 of 15 RMs. ZIKV RNA was most commonly detected in lymph nodes, with 19/45 lymph nodes that were vRNA positive in 5 RMs at 30 dpi. There were 15/45 vRNA positive lymph nodes at 60 dpi and 8/38 at 105 dpi. Reproductive and maternal fetal-interface (MFI) tissues were the second most commonly positive tissues. Twenty-five MFI tissues, including the amniotic/chorionic membrane, decidua, placenta, uterus, and placental bed, were positive, with 10/53 positive at 30 dpi, 14/24 positive at 60 dpi and 1/47 positive at 105 dpi. Other vRNA positive tissues included the primary bronchus, femoral vein, kidney, thyroid, lung, colon, mammary gland, pericardium, hand nerve, and sciatic nerve in 1–2 RMs at one of the three timepoints.

Conclusions

We found ZIKV RNA most frequently within lymph nodes. Lymph nodes are included in lung and small bowel transplants, indicating that these transplants could pose a risk of donor-derived ZIKV transmission. Virus detection within other commonly transplanted tissues, such as the kidney and blood vessels was much less common. We did not determine what fraction of vRNA comes from replication-competent virus in each tissue; some tissues with vRNA might not contain virions that could initiate new infections. Donor-derived Zika virus transmission from other commonly transplanted organs, such as liver, seems unlikely since no viral RNA was detected in this organ.

中文翻译：

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#20：在恒河猴中对寨卡病毒组织嗜性进行建模，以定义供体源性传播的风险

摘要

背景

美国目前有近 115,000 人在等待移植名单上，这大大超过了每年器官捐献者的人数。这种差异强调需要保留所有可能的捐助者。那些最近前往寨卡病毒 (ZIKV) 活跃爆发地区的人通常被取消捐赠者资格，因为免疫抑制的接受者将面临捐赠者源性 ZIKV 感染的风险。因此，我们定义了 ZIKV 组织嗜性和供体源性传播的风险。

方法

我们用波多黎各分离株 ZIKV (PRVABC59) 皮下接种 15 只印度原产恒河猴 (RM)。所有 RM 均在妊娠中期至早期接种。我们在妊娠期间接种，因为血浆病毒血症通常在妊娠期延长，我们希望在长期病毒血症的最坏情况下为供体来源的传播建立组织嗜性模型。在感染后 (dpi) 30、65 和 105 天，对动物实施安乐死并进行全面尸检，每只动物至少评估 60 个组织。ZIKV RNA 在组织中通过 qRT-PCR 定量。

结果

在 15 个 RM 中的 13 个中，血浆病毒血症持续时间 >10 天。ZIKV RNA 最常在淋巴结中检测到，19/45 淋巴结在 30 dpi 时在 5 个 RM 中呈 vRNA 阳性。在 60 dpi 时有 15/45 vRNA 阳性淋巴结，在 105 dpi 时有 8/38。生殖和母体胎儿界面 (MFI) 组织是第二常见的阳性组织。羊膜/绒毛膜、蜕膜、胎盘、子宫和胎盘床等25个MFI组织呈阳性，30 dpi时10/53阳性，60 dpi时14/24阳性，105 dpi时1/47阳性. 其他 vRNA 阳性组织包括初级支气管、股静脉、肾、甲状腺、肺、结肠、乳腺、心包、手神经和坐骨神经，位于三个时间点之一的 1-2 个 RM。

结论

我们在淋巴结中最常发现 ZIKV RNA。淋巴结包括在肺和小肠移植中，表明这些移植可能构成供体源性 ZIKV 传播的风险。在其他常见移植组织（如肾脏和血管）中检测到病毒的情况要少得多。我们没有确定每个组织中有多少 vRNA 来自具有复制能力的病毒；一些带有 vRNA 的组织可能不包含可能引发新感染的病毒粒子。供体来源的寨卡病毒从其他常见移植器官（如肝脏）传播似乎不太可能，因为在该器官中未检测到病毒 RNA。