Growth of Zika virus in human reconstituted respiratory, intestinal, vaginal and neural tissues

Cagno, Valeria; Tseligka, Eirini D.; Bettex, Quentin; Huang, Song; Constant, Samuel; Tapparel, Caroline

doi:10.1016/j.cmi.2019.04.016

Cited by 9 publications

(10 citation statements)

References 15 publications

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“…Compared to transmission by arthropod or contact, this model exclusively supported the possibility of a pathway of feeding transmission and pathology for ZIKV infection. Unexpectedly, we found that the preferential tissue for ZIKV early infection after feeding transmission was the respiratory tissue (lung), but not the stomach or intestine; this is consistent with the ex vivo result that ZIKV can persistently replicate in human respiratory tissues [28], and with the findings of a previous study on oral SIVmac251 infection of infant macaques [29]. Because ZIKV is highly sensitive to acidic pH [28], and the epiglottis is not fully functional at an infantile age [29], the lung might be a feasible entry route for ZIKV.…”

Section: Discussionsupporting

confidence: 89%

Zika virus transmission via breast milk in suckling mice

Pang

Lin

Xin

et al. 2021

Clinical Microbiology and Infection

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Objectives: Infectious Zika viral particles were detected in human milk; however, whether they can be transmitted via breastfeeding remains unknown, so our objective was to clarify this.Methods: Here, in a natural breastfeeding model, wild-type (C57Bl/6; WT) or interferon a/b (IFNa/b) receptor-deficient (A129; KO) murine dams on day 1 post-delivery were infected with Zika virus (ZIKV) intraperitoneally, and the neonates were suckled. In a novel artificial feeding model, WT suckling mice at 1 day old were fed with ZIKV alone or ZIKV and human breast milk mixtures. Thereafter, the virus distribution, clinical progression and neuropathology in the WT or KO neonates were characterized to evaluate the risk of ZIKV transmission through breast milk.Results: In natural breastfeeding, viral RNAs (8/8) and infectious viral particles (7/8) were extensively present in the mammary glands of KO dams. All tested KO neonates (5/5), and none of WT neonates (0/ 9), were infected with ZIKV. In artificial feeding, 100% of the WT neonates (two groups, 12/12 and 16/16) were infected and developed some signs of neurodegeneration. ZIKV tended to seed and accumulate in the lungs and were subsequently disseminated to other tissues in both 16 naturally suckled and 19 artificially fed infected neonates. As human breast milk was mixed with ZIKV and fed to WT neonates, 45% individuals (9/20) were infected; in the infected neonates, the viral spread to the brain was delayed, and the clinical outcomes were alleviated. Conclusions: These results demonstrated that suckling mice can be infected with ZIKV through suckling, and breast milk has potential antiviral activity, inhibiting ZIKV infection.

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Section: Discussionsupporting

confidence: 89%

Zika virus transmission via breast milk in suckling mice

Pang

Lin

Xin

et al. 2021

Clinical Microbiology and Infection

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“…First, although the Asian lineage of the ZIKV strain was the main lineage in recent outbreaks, the African lineage has also shown some serious clinical signs in animals and human reconstituted tissues. 28,37,38 Therefore, to enhance the applicability of this method, the mAb 11C11, which could react with both Asian and African ZIKV strains with low background and good affinity, was selected as the detection antibody. Then, to shorten the infectious time and obtain clear spots, the optimal infectious dose and incubation time were set as 0.0625 MOI/well and 24 h, respectively.…”

Section: ■ Discussionmentioning

confidence: 99%

“…In the past few years, some studies have used it for the detection of neutralizing antibodies against many kinds of viruses (such as EV71, CVA16, CVA10, DENV, HCMV, and so on) due to its highly sensitive, objective, and high-throughput properties. − Here, to develop the Nt-ELISPOT for ZIKV, several factors were optimized. First, although the Asian lineage of the ZIKV strain was the main lineage in recent outbreaks, the African lineage has also shown some serious clinical signs in animals and human reconstituted tissues. ,, Therefore, to enhance the applicability of this method, the mAb 11C11, which could react with both Asian and African ZIKV strains with low background and good affinity, was selected as the detection antibody. Then, to shorten the infectious time and obtain clear spots, the optimal infectious dose and incubation time were set as 0.0625 MOI/well and 24 h, respectively.…”

Section: Discussionmentioning

confidence: 99%

Rapid Neutralization Testing System for Zika Virus Based on an Enzyme-Linked Immunospot Assay

Zhao

Yang

et al. 2019

ACS Infect. Dis.

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Zika virus (ZIKV) is a mosquito-borne flavivirus that has been associated with neuropathology in fetuses and adults, imposing a serious health concern. Therefore, the development of a vaccine is a global health priority. Notably, neutralization tests have a significant value for vaccine development and virus diagnosis. The cytopathic effect (CPE)-based neutralization test (Nt-CPE) is a common neutralization method for ZIKV. However, this method has some drawbacks, such as being time-consuming and labor-intensive and having low-throughput, which precludes its application in the detection of large numbers of specimens. To improve this problem, we developed a neutralization test based on an enzyme-linked immunospot assay (Nt-ELISPOT) for ZIKV and performed the assay in a 96-well format. A monoclonal antibody (mAb), 11C11, with high affinity and reactivity to ZIKV was used to detect ZIKV-infected cells. To optimize this method, the infectious dose of ZIKV was set at a multiplicity of infection (MOI) of 0.0625, and a detection experiment was performed after incubating for 24 h. As a result, under these conditions, the Nt-ELISPOT had good consistency with the traditional Nt-CPE to measure neutralizing titers of sera and neutralizing antibodies. Additionally, three neutralizing antibodies against ZIKV were screened by this method. Overall, we successfully developed an efficient neutralization test for ZIKV that is high-throughput and rapid. This Nt-ELISPOT can potentially be applied to detecting neutralizing titers of large numbers of specimens in vaccine evaluation and neutralizing antibody screening for ZIKV.

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“…Cagno et al 68 investigated the tropism of Asian and African ZIKV strains using human-derived neural, vaginal, intestinal and respiratory tissues. Both ZIKV strains were able to grow in all the tissues tested, although with different efficiencies (7.3 log RNA copies released apically in vaginal tissues versus 9.8 log RNA copies released in intestinal tissues) and without the need of major adaptation.…”

Section: In Vitro Zikv Cellular Models In Fgt Studiesmentioning

confidence: 99%