Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy
Aim of our work was firstly to determine the prevalence of anti-coxsackievirus antibodies during pregnancy. 217 serum samples were tested for antibodies by virus neutralization test against coxsackieviruses (CV) B1–B6, A7 and A9. The second aim was to investigate experimental transmission of virus...
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Інститут молекулярної біології і генетики НАН України
2011
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| Цитувати: | Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy / L. Marosova, M. Sojka, J. Precechtelova, D. Stipalova, M. Badurova, M. Borsanyiova, S. Bopegamage // Вiopolymers and Cell. — 2011. — Т. 27, № 2. — С. 158-161. — Бібліогр.: 16 назв. — англ. |
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irk-123456789-1563732019-06-19T01:24:57Z Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy Marosova, L. Sojka, M. Precechtelova, J. Stipalova, D. Badurova, M. Borsanyiova, M. Bopegamage, S. Short Communications Aim of our work was firstly to determine the prevalence of anti-coxsackievirus antibodies during pregnancy. 217 serum samples were tested for antibodies by virus neutralization test against coxsackieviruses (CV) B1–B6, A7 and A9. The second aim was to investigate experimental transmission of virus to the fetus during pregnancy. Methods. Virus Neutralization Test, RT-PCR. Results. In the serological study, paired blood serum samples from 217 pregnant women were studied for antibodies against coxsackievirus serotypes (CVB1–CVB6, CVA7 and CVA9) in sera of pregnant women from selected areas of the Slovak Republic. Coxsackievirus B4 (CVB4) infection was most prevalent, followed by CVB3, CVA7, CVA9, CVB5, CVB2, CVB1 while coxsackievirus B6 (CVB6) was scarce. In 30 out of 217 cases (13.82 %) current infection was recorded. In the experimental murine study, in the second week of gravidity we observed presence of enteroviral RNA in the placenta and the intestine of the dead fetuses of the mice. Conclusions. Anti-CV antibodies were prevalent in the pregnant mothers indicating circulation of these viruses in the population. Current infection was shown in 13.82 % of studied cases. Presence of virus RNA in the organs of the unborn fetuses in the experimental infection indicates the possibility of transfer of the coxsackievirus B4-E2 infection from mother to child during antenatal development. Keywords: coxsackieviruses, pregnancy. Мета нашої роботи полягала, по-перше, у визначенні розповсюдженості антитіл проти вірусу Коксакі протягом вагітності (217 зразків сироватки крові перевіряли на наявність антитіл проти вирусу Коксакі (ВК) В1–В6, А7 и А9) і, по-друге, у дослідженні передачі вірусу плоду під час вагітності на модельній системі. Методи. Віруснейтралізувальний тест, ОТ-ПЛР. Результати. Проведено серологічне вивчення парних (мати–плід) зразків сироватки крові 217 вагітних жінок з різних районів Словацької Республіки на наявність антитіл проти вірусів Коксакі серотипів (ВКB1–ВКB6, CVA7 и ВКA9). Найпоширенішою інфекцією виявився вірус Коксакі B4 (ВКB4), далі відмічені ВКB3, ВКA7, ВКA9, ВКB5, ВКB2, ВКB1, а інфікування B6 (ВКB6) було найменшим. Інфекцію зареєстровано у 30 з 217 випадків (13,82 %). В експериментах на мишах протягом другого тижня вагітності ми спостерігали присутність ентеровірусної РНК у плаценті і кишечнику мертвих плодів. Висновки. Антитіла проти вирусів Коксакі, знайдені у вагітних жінок, свідчать про розповсюдженість цих вірусів у популяції. Перебіг інфекції показано для 13,82% проаналізованих випадків. Наявність вірусної РНК в органах плодів, які не народилися, за експериментальної інфекції у мишей вказує на можливість передачі вирусів Коксакі B4–E2 інфекції від матері плоду у період дородового розвитку. Ключові слова: віруси Коксакі, вагітність. Цель нашей работы состояла, во-первых, в определении распространенности антител против вируса Коксаки во время беременности (217 образцов сыворотки крови проверяли на наличие антител против вируса Коксаки (ВК) В1–В6, А7 и А9) и, во-вторых, в исследовании передачи вируса плоду во время беременности на модельной системе. Методы. Вируснейтрализующий тест, ОТ-ПЦР. Результаты. Проведены серологическое изучение парных (мать–плод) образцов сыворотки крови 217 беременных женщин из различных районов Словацкой Республики на наличие антител против вирусов Коксаки серотипов (ВКB1–ВКB6, CVA7 и ВКA9). Наиболее распространенной инфекцией оказался вирус Коксаки B4 (ВКB4), далее отмечены ВКB3, ВКA7, ВКA9, ВКB5, ВКB2, ВКB1, а инфицирование B6 (ВКB6) было наименьшим. Инфекция зарегистрирована в 30 из 217 случаев (13,82 %). В экспериментах на мышах в течение второй недели беременности мы наблюдали присутствие энтеровирусной РНК в плаценте и кишечнике мертвых плодов. Выводы. Антитела против вирусов Коксаки, обнаруженные у беременных женщин, свидетельствуют о распространенности этих вирусов в популяции. Протекание инфекции показано для 13,82% проанализированных случаев. Наличие вирусной РНК в органах нерожденных плодов при экспериментальной инфекции у мышей указывает на возможность передачи вирусов Коксаки B4–E2 инфекции от матери плоду в период дородового развития. Ключевые слова: вирусы Коксаки, беременность. 2011 Article Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy / L. Marosova, M. Sojka, J. Precechtelova, D. Stipalova, M. Badurova, M. Borsanyiova, S. Bopegamage // Вiopolymers and Cell. — 2011. — Т. 27, № 2. — С. 158-161. — Бібліогр.: 16 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.000090 http://dspace.nbuv.gov.ua/handle/123456789/156373 612.63 + 578.835.1 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
| language |
English |
| topic |
Short Communications Short Communications |
| spellingShingle |
Short Communications Short Communications Marosova, L. Sojka, M. Precechtelova, J. Stipalova, D. Badurova, M. Borsanyiova, M. Bopegamage, S. Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy Вiopolymers and Cell |
| description |
Aim of our work was firstly to determine the prevalence of anti-coxsackievirus antibodies during pregnancy. 217 serum samples were tested for antibodies by virus neutralization test against coxsackieviruses
(CV) B1–B6, A7 and A9. The second aim was to investigate experimental transmission of virus to the fetus
during pregnancy. Methods. Virus Neutralization Test, RT-PCR. Results. In the serological study, paired
blood serum samples from 217 pregnant women were studied for antibodies against coxsackievirus
serotypes (CVB1–CVB6, CVA7 and CVA9) in sera of pregnant women from selected areas of the Slovak
Republic. Coxsackievirus B4 (CVB4) infection was most prevalent, followed by CVB3, CVA7, CVA9, CVB5,
CVB2, CVB1 while coxsackievirus B6 (CVB6) was scarce. In 30 out of 217 cases (13.82 %) current infection
was recorded. In the experimental murine study, in the second week of gravidity we observed presence of
enteroviral RNA in the placenta and the intestine of the dead fetuses of the mice. Conclusions. Anti-CV antibodies were prevalent in the pregnant mothers indicating circulation of these viruses in the population.
Current infection was shown in 13.82 % of studied cases. Presence of virus RNA in the organs of the unborn
fetuses in the experimental infection indicates the possibility of transfer of the coxsackievirus B4-E2
infection from mother to child during antenatal development.
Keywords: coxsackieviruses, pregnancy. |
| format |
Article |
| author |
Marosova, L. Sojka, M. Precechtelova, J. Stipalova, D. Badurova, M. Borsanyiova, M. Bopegamage, S. |
| author_facet |
Marosova, L. Sojka, M. Precechtelova, J. Stipalova, D. Badurova, M. Borsanyiova, M. Bopegamage, S. |
| author_sort |
Marosova, L. |
| title |
Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy |
| title_short |
Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy |
| title_full |
Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy |
| title_fullStr |
Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy |
| title_full_unstemmed |
Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy |
| title_sort |
coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| publishDate |
2011 |
| topic_facet |
Short Communications |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/156373 |
| citation_txt |
Coxsackievirus infections in pregnant women with a parallel experimental model infection showing possible effects on course of pregnancy / L. Marosova, M. Sojka, J. Precechtelova, D. Stipalova, M. Badurova, M. Borsanyiova, S. Bopegamage // Вiopolymers and Cell. — 2011. — Т. 27, № 2. — С. 158-161. — Бібліогр.: 16 назв. — англ. |
| series |
Вiopolymers and Cell |
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158
SHORT COMMUNICATIONS
Coxsackievirus infections in pregnant women with
a parallel experimental model infection showing
possible effects on course of pregnancy
L. Marosova, M. Sojka, J. Precechtelova, D. Stipalova, M. Badurova,
M. Borsanyiova, S. Bopegamage
1Department of Virology, Slovak Medical University
12, Limbova St., Bratislava, Slovak Republic, 83303
lenka.marosova@szu.sk
Aim of our work was firstly to determine the prevalence of anti-coxsackievirus antibodies during pre-
gnancy. 217 serum samples were tested for antibodies by virus neutralization test against coxsackieviruses
(CV) B1–B6, A7 and A9. The second aim was to investigate experimental transmission of virus to the fetus
during pregnancy. Methods. Virus Neutralization Test, RT-PCR. Results. In the serological study, paired
blood serum samples from 217 pregnant women were studied for antibodies against coxsackievirus
serotypes (CVB1–CVB6, CVA7 and CVA9) in sera of pregnant women from selected areas of the Slovak
Republic. Coxsackievirus B4 (CVB4) infection was most prevalent, followed by CVB3, CVA7, CVA9, CVB5,
CVB2, CVB1 while coxsackievirus B6 (CVB6) was scarce. In 30 out of 217 cases (13.82 %) current infection
was recorded. In the experimental murine study, in the second week of gravidity we observed presence of
enteroviral RNA in the placenta and the intestine of the dead fetuses of the mice. Conclusions. Anti-CV an-
tibodies were prevalent in the pregnant mothers indicating circulation of these viruses in the population.
Current infection was shown in 13.82 % of studied cases. Presence of virus RNA in the organs of the unborn
fetuses in the experimental infection indicates the possibility of transfer of the coxsackievirus B4-E2
infection from mother to child during antenatal development.
Keywords: coxsackieviruses, pregnancy.
Introduction. Enteroviruses are distributed worldwide
with the highest frequency in temperate climate. Their
circulation increases during summer and early autumn
[1]. Enterovirus infections are usually unapparent.
They manifest broad spectrum of symptoms like mild
nonspecific febrile illness or infection of upper respira-
tory tract. In some cases, particularly in newborns or
immunodeficient patients, they may cause serious il-
lnesses like aseptic meningitis, encephalitis and myo-
carditis, they may rarely give rise to serious newborn
sepsis or paralytic poliomyelitis [2–4]. Enteroviruses
also play a role in etiology of chronic illnesses, e. g. di-
lated cardiomyopathy and infections by these viruses
may lead to development of type 1 diabetes (T1D) [5,
6]. These viruses may cause severe or fatal illnesses of
newborns [7]. They have been detected in amniotic
fluid, placenta and in tissue of the fetus [8]. These in-
fections are linked to various congenital anomalies,
stillborn fetuses or abortions [8].
Several experimental infection studies [7, 9, 10]
show effects of coxsackievirus infections on the course
of gravidity, stillbirths, premature birth and higher
ISSN 0233–7657. Biopolymers and Cell. 2011. Vol. 27. N 2. P. 158–161
Institute of Molecular Biology and Genetics NAS of Ukraine, 2011
death rate in female mice infected in later stages of the
gravidity.
Our aim was to study the circulation of coxsa-
ckieviruses in pregnant women, and to investigate pos-
sibility of vertical transmission to the fetus by studying
the presence of enteroviral RNA in the organs of the
stillborn fetuses.
Material and methods. Measurement of antibody
titers in pregnant women by the Virus Neutralization Test
(VNT). Antibodies were detected and measured by the
method described by [11]. Titers of antibodies against
Coxsackieviruses: B1 (CVB1) strain Conn; B2 (CVB2)
strain Ohio; B3 (CVB3) strain Nancy; B4 (CVB4) strain
JVB; B5 (CVB5) strain Faulkner; B6 (CVB6) strain
Schmitt (CVB6); A7 (CVA7) strain Parker, and A9
(CVA9) strain Griggs were determined in paired samples
of sera from gravid women. Rise in antibody titers in the
paired sera showed acute or recent infection.
A 4 fold log2 in paired samples increase of anticoxsa-
ckievirus antibodies by in sera was the marker of the cur-
rent infection.
Detection of viral RNA in the dead fetuses of the
experimental infected gravid mice.
CD-1 female mice were used for experimental in-
fection. Permission for the animal work was obtained
from the Ethics Committee of the Slovak Health Uni-
versity and the State Veterinary and Food Control Au-
thority of the Slovak Republic. 9 pregnant mice were
experimentally infected with CVB4 strain E2. In-
fectious dose of 1⋅107 TCID50 in 0,5 ml suspension of
CVB4-E2 was given as described by [12] by oral
gavage. Female gravid mice were infected during the
three different gestational periods at day 4, 10 and 17.
We selected the pregnant mouse infected with virus in
the second week gestation, which was lethargic and
stopped showing gain in weight, and was sick to give
birth. This mouse was sacrificed, dead fetuses were re-
moved, and organs were studied for presence of RNA.
Detection of viral RNA. RNA Mini Kit («Invitro-
gen», USA) was used for isolation of RNA from prepa-
red organ suspensions. SuperScript™ One-Step RT-
PCR with Platinum® Taq («Invitrogen») kit was used
for the reverse transcription (RT) reaction. Nested reac-
tion was performed using the same kit. The primers, RT
and the nested reaction have been described by [12].
Results and discussion. Most of the seroepide-
miological studies involving CVB infections during
pregnancy are related to their association to T1D. The
involvement of enterovirus infections as an environ-
mental trigger of type 1 diabetes (T1D) and maternal
infection during gravidity increases risk of T1D
development and progress in children in age 0–14 has
been studied by [13, 14]. Serological studies have
shown the presence of anti-CVB IgM antibodies in pre-
gnant women suggesting that coxsackievirus infection
during pregnancy can be the cause of miscarriages and
also linked to development of T1D in children whose
mothers overcame infection during gravidity [15, 16].
Our aim was to analyze the circulation and current
CVB infections in pregnant women. As observed in
Table 1 serotype CVB4 was dominantly circulating in
the studied population, followed by CVB3, CVA9,
CVB5, CVB2 and CVB1. CVB6 prevalence is the least
frequent. Furthermore as seen from Fig. 1: 25.35 % of
the studied cases had already encountered with five of
chosen coxsackievirus serotypes, 1.84 % against all of
studied serotypes and 2.3 % of gravid women did not
have antibodies against any of observed serotype. Cur-
rent infections was noted in 30 out of 217 (13.82 %)
investigated pregnant women.
Transmission of virus from mother to suckling
mice, primarily in later stages of gestation, has been
considered to be possible as shown by [7]. We ob-
served presence of RNA in all the dead fetuses in the
experimentally infected dams in the 2nd week of ges-
tation. Table 2 shows the presence of enteroviral RNA
159
SIGNIFICANCE OF COXSACKIEVIRUS INFECTIONS DURING PREGNANCY
Serotype CVB1 CVB2 CVB3 CVB4 CVB5 CVB6 CVA7 CVA9
+/total 62/217 112/217 148/217 163/217 126/217 21/217 144/217 140/217
Percentage 28.57 51.61 68.20 75.12 58.06 9.68 66.36 64.52
+/total = number of positive sera/total number of sera studied.
Table 1
Prevalence of coxsackievirus serotypes in the studied cases
in the placenta and the navelwort of each of the unborn
fetuses and in intestine of the most of dissected fetuses
of the experimentally infected sick dam. Both were de-
tected by RT-PCR.
The results of our experimental study suggest that
the infection had an effect on the fetuses in the second
week of gestation. Moreover we have shown that virus
may be transferred on the progeny during intrauterinal
development. This aspect should be studied further.
Conclusions. Serological study shows prevalence
of coxsackievirus antibodies in gravid women in
Slovak Republic. Our experimental infection study
shows that the infection in the second week of gestation
and may be a result of transfer of the virus from mother
to fetus. We conclude that systematic follow up of CV
infections and their consequences on the offspring,
fetus and pregnancy should be closely studied. These
studies infer the importance of a possibility of inclu-
ding coxsackieviruses in the screening of the viral in-
fections during pregnancy.
Acknowledgements. Prof. J. M. Galama Nijmgen,
the Netherlands (scientific discussions), Dr. A. Petro-
vicova (for advice in serology), Dr. D. Zelejnkova
SMU Bratislava (veterinary care and advice), MZSR
code: 2005/23-SZU-01, Norwegian financial support
mechanism, Mechanism EEA and Slovak Govern-
ment-Project SK0082.
Л. Ма ро зо ва, М. Сой ка, Я. Пре сеч те ло ва, Д. Стіпа ло ва,
М. Ба ду ро ва, М. Бор сань йо ва, С. Бо пе га ма ге
Інфекції, спри чи нені віру са ми Кок сакі у вагітних, і па ра лель на
ек спе ри мен тальні мо дель інфекції, яка де мо нструє мож ливі
наслідки на пе ребіг вагітності
Ре зю ме
Мета на шої ро бо ти по ля га ла, по-пер ше, у виз на ченні роз пов сюд -
же ності ан титіл про ти вірусу Кок сакі про тя гом вагітності
(217 зразків си ро ват ки крові пе ревіряли на на явність ан титіл
проти ви ру су Кок сакі (ВК) В1–В6, А7 и А9) і, по-дру ге, у до-
слідженні пе ре дачі вірусу пло ду під час вагітності на мо дельній
сис темі. Ме то ди. Вірус ней тралізу валь ний тест, ОТ-ПЛР. Ре -
зуль та ти. Про ве де но се ро логічне вив чен ня пар них (мати–плід)
зразків си ро ват ки крові 217 вагітних жінок з різних ра йонів Сло -
ваць кої Рес публіки на на явність ан титіл про ти вірусів Кок сакі
се ро типів (ВКB1–ВКB6, CVA7 и ВКA9). Най по ши ренішою інфек-
цією ви я вив ся вірус Кок сакі B4 (ВКB4), далі відмічені ВКB3, ВКA7,
ВКA9, ВКB5, ВКB2, ВКB1, а інфіку ван ня B6 (ВКB6) було на й мен -
шим. Інфекцію зареєстро ва но у 30 з 217 ви падків (13,82 %). В екс-
пе ри мен тах на ми шах про тя гом дру го го тиж ня вагітності ми
спос терігали при сутність ен те ровірус ної РНК у пла центі і ки -
шечнику мер твих плодів. Вис нов ки. Антитіла про ти ви русів
Кок сакі, знай дені у вагітних жінок, свідчать про роз пов сюд же-
ність цих вірусів у по пу ляції. Пе ребіг інфекції по ка за но для
13,82% про а налізо ва них ви падків. На явність вірус ної РНК в орга -
нах плодів, які не на ро ди ли ся, за ек спе ри мен таль ної інфекції у ми -
шей вка зує на мож ливість пе ре дачі ви русів Кок сакі B4–E2 інфек-
ції від ма тері пло ду у період до ро до во го роз вит ку.
Клю чові сло ва: віруси Кок сакі, вагітність.
Л. Ма ро зо ва, М. Сой ка, Я. Пре сеч те ло ва, Д. Сти па ло ва,
М. Ба ду ро ва, М. Бор сань йо ва, С. Бо пе га ма ге
Инфек ции, вы зван ные ви ру са ми Кок са ки у бе ре мен ных жен щин,
и па рал лель ная экс пе ри мен таль ная мо дель ин фек ции, по ка зы ва -
ю щая воз мож ные по сле дствия на те че ние бе ре мен нос ти
Ре зю ме
Цель на шей ра бо ты со сто я ла, во-пер вых, в опре де ле нии рас -
прос тра нен нос ти ан ти тел про тив ви ру са Кок са ки во вре мя
бе ре мен нос ти (217 об раз цов сы во рот ки кро ви про ве ря ли на на -
ли чие ан ти тел про тив ви ру са Кок са ки (ВК) В1–В6, А7 и А9) и,
во-вто рых, в ис сле до ва нии пе ре да чи ви ру са пло ду во вре мя бе-
ре мен нос ти на мо дель ной сис те ме. Ме то ды. Ви рус ней тра ли -
зу ю щий тест, ОТ-ПЦР. Ре зуль та ты. Про ве де ны се ро ло ги чес-
кое из уче ние пар ных (мать–плод) об раз цов сы во рот ки кро ви
217 бе ре мен ных жен щин из раз лич ных ра йо нов Сло вац кой Рес -
пуб ли ки на на ли чие ан ти тел про тив ви ру сов Кок са ки се ро ти -
пов (ВКB1–ВКB6, CVA7 и ВКA9). На и бо лее рас прос тра нен ной
ин фек ци ей ока зал ся ви рус Кок са ки B4 (ВКB4), да лее от ме че ны
ВКB3, ВКA7, ВКA9, ВКB5, ВКB2, ВКB1, а ин фи ци ро ва ние B6
(ВКB6) было на и мень шим. Инфек ция за ре гис три ро ва на в 30 из
217 слу ча ев (13,82 %). В экс пе ри мен тах на мы шах в те че ние
вто рой не де ли бе ре мен нос ти мы на блю да ли при су тствие эн -
те ро ви рус ной РНК в пла цен те и ки шеч ни ке мер твых пло дов.
160
MAROSOVA L. ET AL.
Organ Placenta and navelwort Intestine
+/total 16/16 9/11
+/total = number of RT-PCR positive fetus organs/total number of
studied organs.
Table 2
The presence of viral RNA in the fetuses of a gravid mouse infected
in the mid-gestation period of pregnancy
0
5
10
15
20
25
30
0 1 2 3 4 5 6 7 8
Number of detected serotypes
%
Fig. 1. Percentage of sera positive for antibodies against different cox-
sackievirus serotypes in the studied group: x axis – number of detected
serotypes; y – percentage of studied sera (n = 217). Titers of anti-
coxsackievirus antibodies against: none of the serotypes (2,3 %); 1 –
7.83 %; 2 – 10.14 %; 3 – 13.82 %; 4 – 13.82 %; 5 – 25.35 %; 6 –
18.89 %; 7 – 5.99 %; 8 – 1.84 %
Вы во ды. Антитела про тив ви ру сов Кок са ки, об на ру жен ные у
бе ре мен ных жен щин, сви де т ельству ют о рас прос тра нен нос -
ти этих ви ру сов в по пу ля ции. Про те ка ние ин фек ции по ка за но
для 13,82% про а на ли зи ро ван ных слу ча ев. На ли чие ви рус ной
РНК в орга нах не рож ден ных пло дов при экс пе ри мен таль ной
ин фек ции у мы шей ука зы ва ет на воз мож ность пе ре да чи ви ру -
сов Кок са ки B4–E2 ин фек ции от ма те ри пло ду в пе ри од до ро -
до во го раз ви тия.
Клю че вые сло ва: ви ру сы Кок са ки, бе ре мен ность.
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Received 10.01.11
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