- Record: found
- Abstract: found
- Article: found
Fetal loss in pregnant rhesus macaques infected with high-dose African-lineage Zika virus
research-article
Author(s):
Lauren E. Raasch
1 ,
Keisuke Yamamoto
1 ,
Christina M. Newman
1 ,
Jenna R. Rosinski
1 ,
Phoenix M. Shepherd
1 ,
Elaina Razo
2 ,
Chelsea M. Crooks
3 ,
Mason I. Bliss
4 ,
Meghan E. Breitbach
1 ,
Emily L. Sneed
4 ,
Andrea M. Weiler
4 ,
Xiankun Zeng
5 ,
Kevin K. Noguchi
6 ,
Terry K. Morgan
7
,
8 ,
Nicole A. Fuhler
6 ,
Ellie K. Bohm
9 ,
Alexandra J. Alberts
1 ,
Samantha J. Havlicek
1 ,
Sabrina Kabakov
10 ,
Ann M. Mitzey
11 ,
Kathleen M. Antony
12 ,
Karla K. Ausderau
10
,
13 ,
Andres Mejia
4 ,
Puja Basu
4 ,
Heather A. Simmons
4 ,
Jens C. Eickhoff
14 ,
Matthew T. Aliota
9 ,
Emma L. Mohr
2 ,
Thomas C. Friedrich
3
,
4 ,
Thaddeus G. Golos
4
,
9
,
10 ,
David H. O’Connor
1
,
4
,
*
,
,
Dawn M. Dudley
1
Publication date (Electronic):
4 August 2022
Journal:
PLoS Neglected Tropical Diseases
Publisher:
Public Library of Science
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Abstract
Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4–8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques exposed to 1x10 4 PFU (low dose) of African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant rhesus macaques to 1x10 8 PFU (high dose) of African-lineage ZIKV at GD 45 to test the hypothesis that adverse pregnancy outcomes are dose-dependent. Three of eight pregnancies ended prematurely with fetal death. ZIKV was detected in both fetal and placental tissues from all cases of early fetal loss. Further refinements of this exposure system (e.g., varying the dose and timing of infection) could lead to an even more consistent, unambiguous fetal loss phenotype for assessing ZIKV countermeasures in pregnancy. These data demonstrate that high-dose exposure to African-lineage ZIKV causes pregnancy loss in macaques and also suggest that ZIKV-induced first trimester pregnancy loss could be strain-specific.
Author summary
Although pregnant rhesus macaques are susceptible to infection with Zika virus (ZIKV), fetal phenotypes can be subtle and variable. Most macaque studies of ZIKV have involved infection with Asian-lineage viruses because these viruses caused Western Hemisphere outbreaks beginning in 2015. African-lineage ZIKV yields more severe adverse fetal outcomes in small animal models. Here, we provide evidence that pregnant macaques infected late in the first trimester using a high dose of African-lineage ZIKV have frequent ZIKV-associated pregnancy loss. This severe phenotype establishes a new model for evaluating countermeasures and reinforces the idea that African-lineage ZIKV infection may be a cause of pregnancy loss in areas where it is endemic depending on the amount of transmitted virus during infection.
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Most cited references47
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- Article: not found
Zika virus outbreak on Yap Island, Federated States of Micronesia.
Mark Duffy, Tai-Ho Chen, W. Thane Hancock … (2009)
In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented. We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus. We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified. This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission. 2009 Massachusetts Medical Society
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- Abstract: found
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Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007
Robert Lanciotti, Olga Kosoy, Janeen Laven … (2008)
Zika virus (ZIKV) is a mosquito-transmitted virus in the family Flaviviridae and genus Flavivirus. It was initially isolated in 1947 from blood of a febrile sentinel rhesus monkey during a yellow fever study in the Zika forest of Uganda ( 1 ). The virus was subsequently isolated from a pool of Aedes africanus mosquitoes collected in 1948 from the same region of the Zika forest; a serologic survey conducted at that time showed that 6.1% of the residents in nearby regions of Uganda had specific antibodies to ZIKV ( 1 , 2 ). Over the next 20 years, several ZIKV isolates were obtained from Aedes spp. in Africa (Ae. africanus) and Malaysia (Ae. aegypti), implicating these species as likely epidemic or enzootic vectors ( 3 – 5 ). Several ZIKV human isolates were also obtained in the 1960s and 1970s from East and West Africa during routine arbovirus surveillance studies in the absence of epidemics ( 6 – 8 ). Additional serologic studies in the 1950s and 1960s detected ZIKV infections among humans in Egypt, Nigeria, Uganda, India, Malaysia, Indonesia, Pakistan, Thailand, North Vietnam, and the Philippines ( 5 ). These data strongly suggest widespread occurrence of ZIKV from Africa to Southeast Asia west and north of the Wallace line. In 1977, ZIKV infection was confirmed among 7 patients in central Java, Indonesia, during an acute fever study ( 9 ). Data on these 7 ZIKV cases and several previously reported human infections indicated that clinical characteristics of infection with ZIKV included fever, headache, malaise, stomach ache, dizziness, anorexia, and maculopapular rash; in all cases infection appeared relatively mild, self-limiting, and nonlethal ( 6 , 8 – 10 ). In April 2007, an epidemic of rash, conjunctivitis, and arthralgia was noted by physicians in Yap State, Federated States of Micronesia ( 11 ). Laboratory testing with a rapid assay suggested that a dengue virus (DENV) was the causative agent. In June 2007, samples were sent for confirmatory testing to the Arbovirus Diagnostic Laboratory at the Centers for Disease Control and Prevention (CDC, Fort Collins, CO, USA). Serologic testing by immunoglobulin (Ig) M–capture ELISA with DENV antigen confirmed recent flavivirus infection in several patients. Testing by reverse transcription–PCR (RT-PCR) with flavivirus consensus primers generated DNA fragments, which when subjected to nucleic acid sequencing, demonstrated ≈90% nucleotide identity with ZIKV. These findings indicated that ZIKV was the causative agent of the Yap epidemic. We report serologic parameters of the immune response among ZIKV-infected humans, data on estimated levels of viremia, and the complete coding region nucleic acid sequence of ZIKV associated with this epidemic. Methods Analysis of Patient Samples Details of the epidemic, including clinical and laboratory findings for all patients, will be reported elsewhere (M.R. Duffy et al., unpub. data). A subset of ZIKV-infected patients for whom acute- and convalescent-phase paired serum specimens had been collected was analyzed by using several serologic assays to evaluate the extent of cross-reactivity to several related flaviviruses. Patients were classified as primary flavivirus/ZIKV infected or secondary flavivirus/ZIKV probable infected. Primary flavivirus/ZIKV–infected patients were those in whom acute-phase serum specimens ( 1 heterologous flaviviruses in their acute-phase specimen and were also IgM positive for ZIKV in their acute-phase specimen, or IgM and IgG positive for ZIKV in their convalescent-phase specimen. The designation “ZIKV probable” was used because secondary flavivirus infections demonstrate extensive cross-reactivity with other flaviviruses, and in some cases, higher serologic reactivity to the original infecting flavivirus (“original antigenic sin” phenomenon). Thus, in secondary flavivirus infections shown in Tables 1 and 2, serologic data alone is insufficient to confirm ZIKV as the recently infecting flavivirus. However, these secondary flavivirus/ZIKV probable infections were likely recent ZIKV infections because ZIKV was the only virus detected during the epidemic in Yap, a relatively small and isolated island ( 11 ). Table 1 IgG and IgM testing with heterologous flaviviruses of patients infected with ZIKV, Yap State, Micronesia, 2007* Patient Days after onset IgG IgM ZIKV ZIKV DENV YFV JEV MVEV WNV Primary flavivirus ZIKV 822a 5 1.5 23.2 1.3 1.4 1.7 1.1 – 822b 10 1.2 39.5 1.2 1.0 2.4 1.2 – 822c 24 3.3 13.1 2.7 0.63 1.8 1.3 – 830a 2 1.1 1.3 4.4 0.48 4.4 2.9 – 830b 21 1.8 16.3 1.9 0.63 1.3 1.6 – 849a 3 1.5 4.5 0.92 0.95 1.2 0.66 – 849b 18 3.0 18.2 2.2 1.0 2.7 1.5 – 862a 6 1.9 25.4 1.7 1.1 1.8 1.0 – 862b 20 2.6 15.4 2 1.1 2.3 1.1 Eq Secondary flavivirus ZIKV (probable) 817a 1 5.9 1.4 1.7 0.8 1.7 0.7 – 817b 19 5.7 8.1 5.1 2.1 1.7 1.0 – 833a 1 3.4 1.7 3.7 1.0 2.8 1.3 – 833b 19 8.2 3.1 2.3 0.9 2.5 1.3 – 844a 2 3.8 3.8 6.8 2.0 21.5 0.7 – 844b 16 8.5 12.7 14.9 7.0 42.9 1.6 – 955a 1 5.0 1.8 3.7 1.0 3.4 2.4 Eq 955b 14 26.6 10.9 3.4 0.8 1.7 4.0 Eq 968a 1 4.0 1.7 1.3 0.6 1.2 1.2 – 968b 3 12.3 20.4 2.9 0.8 0.9 2.0 – 839a 3 1 0.92 3.4 0.7 2.7 2.1 – 839b 20 4.9 17.2 2.2 2.1 1.9 1.8 – 847a 5 0.9 0.94 4.1 4.1 2.3 1.3 – 847b 8 14.1 21.5 1.4 3.3 1.1 2.6 – *Ig, immunoglobulin; ZIKV, Zika virus; DENV, dengue virus type 1–4 mixture; YFV, yellow fever virus; JEV, Japanese encephalitis virus; MVEV, Murray Valley encephalitis virus; WNV, West Nile virus; –, negative. Eq, result in equivocal range of the assay. IgG and IgM testing was conducted by ELISA except for WNV, which was tested by microsphere assay; ELISA values are patient optical densities divided by negative control optical densities; 3 positive. Table 2 Neutralization testing with heterologous flaviviruses of patients infected with ZIKV, Yap State, Micronesia, 2007* Patient Days after onset PRNT90 titer ZIKV DENV1 DENV2 DENV3 DENV4 JEV YFV WNV SLEV MVEV Primary flavivirus ZIKV 822a 5 320 3 were considered positive, and values 2–3 were considered equivocal. Neutralizing antibody titers were determined by using a PRNT with a 90% cut-off value ( 15 ). Real-Time RT-PCR Two real-time primer/probe sets specific for the ZIKV 2007 strain were designed by using ZIKV 2007 nucleotide sequence data in the PrimerExpress software package (Applied Biosystems, Foster City, CA, USA). Primers were synthesized by Operon Biotechnologies (Huntsville, AL, USA) with 5-FAM as the reporter dye for the probe (Table 3). All real-time assays were performed by using the QuantiTect Probe RT-PCR Kit (QIAGEN, Valencia, CA, USA) with amplification in the iCycler instrument (Bio-Rad, Hercules, CA, USA) following the manufacturer’s protocol. Specificity of the ZIKV primers was evaluated by testing the following viral RNAs, all of which yielded negative results: DENV-1, DENV-2, DENV-3, DENV-4, WNV, St. Louis encephalitis virus, YFV, Powassan virus, Semliki Forest virus, o’nyong-nyong virus, chikungunya virus, and Spondweni virus (SPOV). Table 3 Description and performance characteristics of Zika virus real-time RT-PCR primer/probe sets* Primer Genome position† Sequence (5′ → 3′) Sensitivity, no. copies Specificity‡ ZIKV 835 835–857 TTGGTCATGATACTGCTGATTGC ZIKV 911c 911–890 CCTTCCACAAAGTCCCTATTGC 100 ZIKV ZIKV 860-FAM 860–886 CGGCATACAGCATCAGGTGCATAGGAG ZIKV 1086 1086–1102 CCGCTGCCCAACACAAG ZIKV 1162c 1162–1139 CCACTAACGTTCTTTTGCAGACAT 25 ZIKV ZIKV 1107-FAM 1107–1137 AGCCTACCTTGACAAGCAGTCAGACACTCAA *RT-PCR, reverse transcription–PCR; ZIKV, Zika virus.
†Based on ZIKV MR 766 GenBank accession no. AY632535.
‡ZIKV specificity indicates a positive result with ZIKV only and no reactivity with dengue virus-1 (DENV-1), DENV-2, DENV-3, DENV-4, West Nile virus, St. Louis encephalitis virus, yellow fever virus, Powassan virus, Semliki Forest virus, o’nyong-nyong virus, chikungunya virus, and Spondweni virus. Sensitivity of the ZIKV real-time assay was evaluated by testing dilutions of known copy numbers of an RNA transcript copy of the ZIKV 2007 sequence. Copy numbers of RNA were determined by using the Ribogreen RNA-specific Quantitiation Kit (Invitrogen) and the TBE-380 mini-fluorometer (Turner Biosystems, Sunnyvale, CA, USA). RNA transcripts ranging from 16,000 to 0.2 copies were tested in quadruplicate to determine the sensitivity limit and to construct a standard curve for estimating the genome copy number of ZIKV in patient samples. All serum samples obtained during the epidemic were tested for ZIKV RNA by using this newly designed real-time RT-PCR. Concentration of viral RNA (copies/milliliter) was estimated in ZIKV-positive patients by using the standard curve calculated by the iCycler instrument (Table 4). All RT-PCR–positive specimens were placed on monolayers of Vero, LLC-MK2, and C6/36 cells to isolate virus; no specimens showed virus replication. Table 4 Results of quantitative real-time RT-PCR of samples from ZIKV-positive patients, Yap State, Micronesia, 2007* Patient Days after onset ZIKV real-time RT-PCR Ct-860† Ct-1107† Result Estimated copies/mL‡ 824 1 34.3 34.7 + 11,647 939 2 32.0 32.4 + 67,817 947 2 34.3 33.9 + 21,495 949 2 35.1 35.1 + 8,573 969 1 29.4 29.3 + 728,800 037 1 32.1 32.5 + 62,816 830a 2 30.7 30.0 + 426,325 847a 5 34.8 34.7 + 11,647 950a 0 32.2 32.7 + 53,894 943 3 37.6 35.6 + 5,845 952 1 29.3 29.5 + 625,280 958 11 29.9 30.3 + 338,797 970 1 35.5 34.8 + 10,788 42 0 32.9 33.6 + 27,048 941 3 31.1 38.0 + 930 964 0 38.3 37.6 + 1,263 063a 2 37.5 38.0 + 930 *RT-PCR, reverse transcription–PCR; ZIKV, Zika virus; Ct, crossing threshold; +, positive.
†Ct values with primer set 835/911c/860-FAM or 1086/1162c/1107-FAM. Values 1 of the heterologous flaviviruses tested, and all demonstrated low levels of cross-reactive IgM as shown by a P/N value in the equivocal range. PRNT90 results showed that among secondary flavivirus/ZIKV–probable patients, the neutralizing antibody response was higher to ZIKV and more cross-reactive, a finding commonly observed among secondary flavivirus infections. A >4-fold PRNT90 titer between ZIKV and heterologous flaviviruses was observed in only 3 of the 7 patients. In all other cases, the PRNT difference between ZIKV and other flaviviruses tested was 38.5, which suggests either a false-positive result or a sample with low levels of ZIKV RNA below the defined cut-off of the assay. Table 4 shows estimated viral concentrations of the 17 ZIKV-positive specimens. The viral RNA concentrations were ≈900–729,000 copies/mL. Most (15 of 17) of the ZIKV-positive samples were from specimens collected 2 patients; in these overlap regions the sequence identity between different patients was ≈100%. Only 2-nt differences between patients were noted within the overlapping regions, strongly suggesting that 1 ZIKV strain circulated during the epidemic. Percentage identity over the entire coding region of ZIKV 2007 EC sequence, when compared with the prototype ZIKV (MR 766, isolated in 1947), was 88.9% and 96.5% at the nucleotide and amino acid levels, respectively. Phylogenetic trees constructed from the complete coding region of all available flaviviruses generated by a variety of methods (neighbor-joining, maximum-parsimony, or minimum-evolution) showed the same overall topology, with the ZIKV prototype and 2007 EC virus placed in a unique clade (clade 10) within the mosquito-borne flavivirus cluster previously described by Kuno et al. ( 16 ). Alignment with phylogenetic tree construction by neighbor-joining, maximum-parsimony, or minimum-evolution algorithms was also performed for the NS5 region of all available flaviviruses because extensive sequencing and phylogenetic analysis have been conducted for this region ( 16 ). Three additional ZIKV strains isolated from Senegal in 1984 and sequenced in this study were also included in a tree. This NS5 tree demonstrated similar topology to the complete coding region tree, with all ZIKVs placed within a unique clade (clade 10) along with SPOV. Figure 1 shows the NS5 tree with only mosquito-borne flaviviruses (cluster) displayed. This NS5 tree also shows that within the Zika/Spondweni clade there appear to be 3 branches among ZIKVs: Nigerian ZIKVs, prototype MR766, and 2007 Yap virus. Percentage identity among these ZIKVs confirms the tree topology, in which ZIKV 2007 EC is most distally related to East and West African ZIKV strains (data not shown). The predicted amino acid sequence of ZIKV 2007 EC contains the Asn-X-Ser/Thr glycosylation motif at position 154 in the envelope glycoprotein, found in many flaviviruses, yet absent by deletion in the prototype ZIKV MR 766. This region of the prototype virus, along with 3 ZIKVs isolated from Senegal in 1984, was sequenced (Figure 2). Included in this alignment is a ZIKV isolate from GenBank (accession no. AF372422). Sequencing confirmed that prototype ZIKV MR766 has a 4-aa (12-nt) deletion when compared with ZIKV 2007 EC virus and ZIKVs from Senegal. Figure 2 Alignment of nucleotide and amino acid sequences adjacent to the envelope (ENV)–154 glycosylation site of Zika virus strains. Dashes indicate deletions. EC, epidemic consensus. Discussion Historically, ZIKV has rarely been associated with human disease, with only 1 small cluster of human cases in Indonesia reported ( 9 ). We report a widespread epidemic of human disease associated with ZIKV in Yap State in 2007. ZIKV epidemics may have occurred but been misdiagnosed as dengue because of similar clinical symptoms and serologic cross-reactivity with DENVs. Our serologic data indicate that ZIKV-infected patients can be positive in an IgM assay for DENVs, particularly if ZIKV is a secondary flavivirus infection. If ZIKV is the first flavivirus encountered, our data indicate that cross-reactivity is minimal. However, when ZIKV infection occurs after a flavivirus infection, our data indicate that the extent of cross-reactivity in the IgM assay is greater. Therefore, if ZIKV infections occur in a population with DENV (or other flavivirus) background immunity, our data suggest that extensive cross-reactivity in the dengue IgM assay will occur, which could lead to the erroneous conclusion that dengue caused the epidemic. Whether this cross-reactivity has occurred is open to speculation. However, reexamination of specimens from dengue epidemics may provide an answer. In addition, use of virus isolation or RT-PCR for laboratory diagnosis of dengue infections would also prevent this misinterpretation. Therefore, use of virus detection assays in dengue epidemics should be a component of laboratory testing algorithms. Levels of viremia among ZIKV-infected patients were relatively low. Unfortunately, measurement of concentration of infectious ZIKV was not possible because a virus isolate was not obtained from any patient during the epidemic. Absence of a ZIKV 2007 isolate also precluded use of a ZIKV 2007 isolate to generate a standard curve in the RT-PCR, which in turn could have estimated the concentration of infectious virus within patients. An estimation of the number of genome copies circulating in ZIKV-infected patients was calculated by using an RNA transcript and provides some indication of infectious virus concentration in ZIKV-infected patients. If one assumes a ratio range of 200–500 genome copies per infectious virus particle, a range reported for several flaviviruses, then the copies/milliliter values in Table 4 would be in the range of ≈2–3,500 infectious virus particles/mL, with only 4 specimens in which ZIKV exceeded 1,000 infectious units/mL ( 18 , 19 ). These findings may partially explain why ZIKV was not isolated, especially if one considers that shipping samples to our laboratory took ≈1 week, and shipping conditions were not conducive to virus isolation. These concentration estimates are also consistent with those of a study in which a ZIKV-infected human volunteer showed low viremia; virus was isolated only on day 4, and the volunteer was unable to infect Ae. aegypti mosquitoes that fed on the patient during the acute stage of disease ( 10 ). Although generation of a complete coding region nucleic acid sequence by using a combination of patient samples from the epidemic is an unconventional approach, it was performed out of necessity because of limited volumes of patient samples. However, the extent of agreement among overlapping regions confirms that the sequence obtained accurately represents the virus associated with the epidemic. Nucleic acid sequence of ZIKV 2007 showed divergence (11%) from the prototype strain (MR766) isolated in 1947. However, the predicted amino acid sequence is fairly conserved (96%), which is likely the result of the selective pressure maintained on the virus because replication occurs in vertebrate hosts and arthropod vectors. Phylogenetic trees based on the complete coding region or the NS5 region confirm results of a study in which ZIKV was classified in a unique clade among the mosquito-borne flaviviruses and most closely related to SPOV ( 16 ). The NS5 mosquito-borne flavivirus tree (Figure 1), which includes additional ZIKV isolates, confirms these relationships and suggests that there are 3 subclades among ZIKV isolates that reflect geographic origin. Senegal ZIKVs and prototype virus from Uganda may represent West and East African lineages, respectively. The 2007 ZIKV is distantly related to these 2 African subclades and may represent divergence from a common ancestor with spread throughout Southeast Asia and the Pacific. Human ZIKV cases were detected in peninsular Malaysia in 1980, which confirms that ZIKV was active in this region before 2007 ( 9 ). Additional sequence analysis of other temporally and geographically distinct ZIKV strains is needed to further elucidate relationships among these viruses. Of particular interest is an additional 12 nt in the envelope gene (corresponding to 4 aa) in our ZIKV isolate that were not present in the ZIKV prototype virus (Figure 2). This difference is noteworthy because these 4 aa correspond to the envelope protein 154 glycosylation motif found in many flaviviruses and associated in some instances with virulence. This glycosylation motif is also absent because of a 6-aa deletion in the ZIKV isolate obtained from GenBank (accession no. AF372422); however, the geographic and temporal origins of this virus were not available. Loss of the envelope protein 154 glycoslyation site has been observed in some flaviviruses, and in the case of Kunjin virus has been shown to occur during passage. However, with Kunjin virus, the glycosylation site motif was lost because of a 1-base mutation, rather than a deletion, that altered the N-X-S/T sequon ( 20 ). Loss of this glycosylation site by a 4-aa deletion has also been observed in several lineage-2 WNV strains when compared with all other WNV strains ( 21 ). The glycoslyation motif in WNV may be lost during extensive mouse brain passage; however, no direct evidence exists to support this hypothesis ( 21 ). This process may occur in ZIKV; the glycoslyation motif in MR 766 may have been present in earlier passages of prototype MR766 and lost during extensive mouse brain passage. However, earlier passage strains of MR766 were not available for investigating this hypothesis. Alternatively, the presence or absence of this glycosylation motif may represent an ancient evolutionary event with subsequent divergence of 2 ZIKV types with or without the E-154 glycosylation site amino acids. Sequence data derived from 3 additional ZIKV isolates from Senegal showed that glycosylation is intact in these isolates, which suggests evolutionary divergence. More extensive sequence analysis of available ZIKV strains of various temporal, geographic, and passage histories may provide some insight into this issue.
- Record: found
- Abstract: not found
- Article: not found
Zika Virus and Birth Defects--Reviewing the Evidence for Causality.
Author and article information
Contributors
Lauren E. Raasch:
ORCID: https://orcid.org/0000-0003-0280-3678
Role: Data curationRole: InvestigationRole: ResourcesRole: VisualizationRole: Writing
– original draftRole: Writing – review & editing
Keisuke Yamamoto: Role: InvestigationRole: Writing – original draft
Christina M. Newman: Role: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole:
ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
Jenna R. Rosinski: Role: Data curationRole: InvestigationRole: ResourcesRole: VisualizationRole: Writing
– original draft
Phoenix M. Shepherd: Role: InvestigationRole: Resources
Elaina Razo: Role: Data curationRole: InvestigationRole: ResourcesRole: Visualization
Chelsea M. Crooks: Role: MethodologyRole: ResourcesRole: Writing – review & editing
Mason I. Bliss: Role: Investigation
Meghan E. Breitbach: Role: Data curationRole: InvestigationRole: MethodologyRole: Resources
Emily L. Sneed: Role: Resources
Andrea M. Weiler: Role: Investigation
Xiankun Zeng: Role: Investigation
Kevin K. Noguchi: Role: Investigation
Terry K. Morgan: Role: Investigation
Nicole A. Fuhler: Role: Investigation
Ellie K. Bohm: Role: Investigation
Alexandra J. Alberts: Role: InvestigationRole: Visualization
Samantha J. Havlicek: Role: InvestigationRole: Visualization
Sabrina Kabakov: Role: Data curationRole: Investigation
Ann M. Mitzey: Role: Resources
Kathleen M. Antony: Role: InvestigationRole: MethodologyRole: Resources
Karla K. Ausderau: Role: InvestigationRole: MethodologyRole: Writing – original draft
Andres Mejia: Role: InvestigationRole: Resources
Puja Basu: Role: InvestigationRole: Resources
Heather A. Simmons: Role: InvestigationRole: ResourcesRole: Writing – review & editing
Jens C. Eickhoff: Role: Formal analysis
Matthew T. Aliota: Role: ConceptualizationRole: Funding acquisitionRole: Investigation
Emma L. Mohr: Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole:
Writing – original draft
Thomas C. Friedrich: Role: ConceptualizationRole: Funding acquisitionRole: Methodology
Thaddeus G. Golos: Role: ConceptualizationRole: Funding acquisitionRole: Methodology
David H. O’Connor:
ORCID: https://orcid.org/0000-0003-2139-470X
Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole:
Writing – review & editing
Dawn M. Dudley: Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole:
Project administrationRole: SupervisionRole: ValidationRole: Writing – original draft
Michael R. Holbrook: Role: Editor
Journal
Journal ID (nlm-ta): PLoS Negl Trop Dis
Journal ID (iso-abbrev): PLoS Negl Trop Dis
Journal ID (publisher-id): plos
Title:
PLoS Neglected Tropical Diseases
Publisher:
Public Library of Science
(San Francisco, CA USA
)
ISSN
(Print):
1935-2727
ISSN
(Electronic):
1935-2735
Publication date
(Electronic):
4
August
2022
Publication date Collection:
August
2022
Volume: 16
Issue: 8
Electronic Location Identifier: e0010623
Affiliations
[1
]
Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, United
States of America
[3
]
Department of Pathobiological Sciences, UW Madison, Madison, Wisconsin, United States
of America
[4
]
Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, United
States of America
[5
]
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick,
Maryland, United States of America
[6
]
Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri,
United States of America
[7
]
Department of Pathology, Oregon Health and Science University, Portland, Oregon, United
States of America
[8
]
Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland,
Oregon, United States of America
[9
]
Department of Veterinary and Biomedical Sciences, University of Minnesota, Minneapolis,
Minnesota, United States of America
[10
]
Department of Kinesiology Occupational Therapy Program, University of Wisconsin Madison,
Madison, Wisconsin, United States of America
[11
]
Department of Comparative Biosciences, UW Madison, Madison, Wisconsin, United States
of America
[12
]
Department of Obstetrics and Gynecology, UW Madison, Madison, Wisconsin, United States
of America
Author notes
[¤a]
Current address: Touro College of Osteopathic Medicine, New York City, New York, United States of America
* E-mail:
dhoconno@
123456wisc.edu
Author information
Lauren E. Raasch
https://orcid.org/0000-0003-0280-3678
David H. O’Connor
https://orcid.org/0000-0003-2139-470X
Article
Publisher ID: PNTD-D-22-00439DOI: 10.1371/journal.pntd.0010623
PMC ID: 9380952
PubMed ID: 35926066
SO-VID: 324183c5-a69d-4859-934f-0ef13651cb4f
Copyright © © 2022 Raasch et al
License:
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
History
Date
received
: 13
April
2022
Date
accepted
: 29
June
2022
Page count
Figures: 7,
Tables: 2,
Pages: 24
Funding
Funded by:
funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
Award ID: K08AI139341
Award Recipient
:
Emma L. Mohr
Funded by:
funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
Award ID: R01AAH9849
Award Recipient
:
Emma L. Mohr
Funded by:
funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
Award ID: R01AI132563
Award Recipient
:
Thomas C. Friedrich
Funded by:
funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
Award ID: 5P01AI132132
Award Recipient
:
ORCID: https://orcid.org/0000-0003-2139-470X
David H. O’Connor
Funded by:
funder-id http://dx.doi.org/10.13039/100000071, National Institute of Child Health and Human Development;
Award ID: P50HD103525
Award Recipient
:
Kevin K. Noguchi
Funding for this project came from the following sources: National Institute of Allergy
and Infectious Diseases grant K08AI139341 (ELM)(
https://www.niaid.nih.gov/), National Institute of Allergy and Infectious Diseases grant R01AAH9849 (ELM and
KA)(
https://www.niaid.nih.gov/), National Institute of Allergy and Infectious Diseases grant R01AI132563 (MTA and
TCF)(
https://www.niaid.nih.gov/), National Institutes of Health grant 5P01AI132132 (DHO)(
https://www.nih.gov/), National Institute of Child Health & Human Development grant P50HD103525 (KKN)(
https://www.nichd.nih.gov/). The funders had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
Categories
Subject:
Research Article
Subject:
Biology and life sciences
Subject:
Organisms
Subject:
Eukaryota
Subject:
Animals
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Vertebrates
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Amniotes
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Mammals
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Primates
Subject:
Monkeys
Subject:
Old World monkeys
Subject:
Macaque
Subject:
Biology and life sciences
Subject:
Zoology
Subject:
Animals
Subject:
Vertebrates
Subject:
Amniotes
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Mammals
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Primates
Subject:
Monkeys
Subject:
Old World monkeys
Subject:
Macaque
Subject:
Biology and life sciences
Subject:
Organisms
Subject:
Viruses
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RNA viruses
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Flaviviruses
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Zika Virus
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Biology and Life Sciences
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Microbiology
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Medical Microbiology
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Microbial Pathogens
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Viral Pathogens
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Flaviviruses
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Zika Virus
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Medicine and Health Sciences
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Pathology and Laboratory Medicine
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Pathogens
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Microbial Pathogens
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Viral Pathogens
Subject:
Flaviviruses
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Zika Virus
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Biology and Life Sciences
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Organisms
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Viruses
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Viral Pathogens
Subject:
Flaviviruses
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Zika Virus
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Medicine and Health Sciences
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Women's Health
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Embryology
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Placenta
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Biology and Life Sciences
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Reproductive System
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Placenta
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Medicine and Health Sciences
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Anatomy
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Reproductive System
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Placenta
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Research and Analysis Methods
Subject:
Animal Studies
Subject:
Experimental Organism Systems
Subject:
Animal Models
Subject:
Rhesus Monkeys
Subject:
Biology and life sciences
Subject:
Organisms
Subject:
Eukaryota
Subject:
Animals
Subject:
Vertebrates
Subject:
Amniotes
Subject:
Mammals
Subject:
Primates
Subject:
Monkeys
Subject:
Old World monkeys
Subject:
Macaque
Subject:
Rhesus Monkeys
Subject:
Biology and life sciences
Subject:
Zoology
Subject:
Animals
Subject:
Vertebrates
Subject:
Amniotes
Subject:
Mammals
Subject:
Primates
Subject:
Monkeys
Subject:
Old World monkeys
Subject:
Macaque
Subject:
Rhesus Monkeys
Subject:
Biology and Life Sciences
Subject:
Developmental Biology
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Embryology
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Fetuses
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Biology and Life Sciences
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Microbiology
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Virology
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Viral Transmission and Infection
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Viral Load
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Biology and Life Sciences
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Anatomy
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Body Fluids
Subject:
Blood
Subject:
Blood Plasma
Subject:
Medicine and Health Sciences
Subject:
Anatomy
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Body Fluids
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Blood
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Blood Plasma
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Biology and Life Sciences
Subject:
Physiology
Subject:
Body Fluids
Subject:
Blood
Subject:
Blood Plasma
Custom metadata
PLOS Publication Stage vor-update-to-uncorrected-proof
Publication Update 2022-08-16
Data Availability All relevant data are within the manuscript and its
Supporting information files. Primary data that support this study are also available at the Zika Open Research
Portal (
https://openresearch.labkey.com/project/ZEST/begin.view). Data for the high-dose ZIKV-DAK-infected cohort can be found under study ZIKV-046;
data for the low-dose ZIKV-DAK infected cohort can be found under study ZIKV-030,
ZIKV-PR and mock-inoculated cohorts can be found under ZIKV-044.
ScienceOpen disciplines: Infectious disease & Microbiology
Data availability:
ScienceOpen disciplines: Infectious disease & Microbiology