Multiple Human Papillomavirus Types Replicate in 3A Trophoblasts

You, Hong; Liu, Y.; Agrawal, Nalini; Prasad, C. Krishna; Edwards, J. L.; Osborne, Aileen; Korourian, Soheila; Lowery, Curtis L.; Hermonat, Paul L.

doi:10.1016/j.placenta.2007.08.005

Cited by 55 publications

(58 citation statements)

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“…However, strong cytoplasmic L1 capsid protein mRNA expression has also been reported in a trophoblast cell culture experimentally infected with HPV. 20 Moreover, cytoplasmic localization of HPV has been reported using both HPV L1 IHC and CISH 25,27,[51][52][53] and this pattern may be characteristic of HPV infection in the trophoblast. We also observed an appropriate host response of DNA damage/repair and p53 activation, which was consistent with that previously described for papillomavirus infection.…”

Section: Discussionmentioning

confidence: 99%

“…7,11,[14][15][16][17] HPV strains 6,11,16,18, and 31 have been shown to replicate in trophoblast cell lines, [18][19][20] where HPV infection decreased trophoblast number and trophoblast-endometrial cell adhesion in vitro. 19,20 We investigated for the presence of HPV in the placenta and carried out a histopathological and molecular cross-sectional study of 339 placentae from complicated and uncomplicated pregnancies. We sought to determine if the HPV infection occurred in the placenta, the histopathological features, the correlation with uterine cervical smear history, and if it could contribute to pregnancy complications.…”

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confidence: 99%

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A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

et al. 2015

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Viral infections are known to adversely affect pregnancy, but scant attention has been given to human papilloma virus (HPV) infection. We aimed to determine the molecular and histopathological features of placental HPV infection, in association with pregnancy complications including fetal growth restriction, pre-maturity, pre-eclampsia, and diabetes. Three hundred and thirty-nine placentae were selected based on the presence or absence of pregnancy complications. Five independent methods were used to identify HPV in the placenta, namely, immunohistochemistry for L1 viral capsid, in situ hybridization to high-risk HPV DNA, PCR, western blotting, and transmission electron microscopy. Pregnancy complications and uterine cervical smear screening results were correlated with placental HPV histopathology. In this study, which was deliberately biased towards complications, HPV was found in the decidua of 75% of placentae (253/339) and was statistically associated with histological acute chorioamnionitis (P o0.05). In 14% (35/253) of the HPV positive cases, HPV L1 immunoreactivity also occurred in the villous trophoblast where it was associated with a lymphohistiocytic villitis (HPV-LHV), and was exclusively of high-risk HPV type. HPV-LHV significantly associated with fetal growth restriction, preterm delivery, and pre-eclampsia (all P o0.05). All cases of pre-eclampsia (20/20) in our cohort had high-risk placental HPV. A further 55 cases (22%, 55/253) of HPV positive placentae had minimal villous trophoblast HPV L1 immunoreactivity, but a sclerosing pauci-immune villitis, statistically associated with diabetes (49.1%, 27/55, Po 0.05). For women with placental HPV, 33% (69/207) had an HPV-related positive smear result before pregnancy compared with (9.4% 8/85) of women with HPV-negative placentae (P = 0.0001). Our findings support further investigations to determine if vaccination of women and men will improve pregnancy outcomes. Modern Pathology (2015Pathology ( ) 28, 1369Pathology ( -1382 doi:10.1038/modpathol.2015 published online 21 August 2015 In the immune and hormonal modulated milieu of pregnancy, viruses are well known to infect the placenta, developing fetus, and neonate. The most common and important neoplastic driver of the lower uterine tract, human papillomavirus (HPV), 1 has been detected in the uterine cervix of 15-25% of pregnant women 2-6 and a cervical HPV infection during pregnancy has been associated with a higher incidence of spontaneous abortions, 7-9 premature rupture of the membranes, 10 spontaneous preterm labor, 11,12 pre-eclampsia, 13 and placental 'villitis' not otherwise specified. 12 HPV DNA has been detected in the placenta and amniotic fluid. 7,11,[14][15][16][17]11,16,18,and 31 have been shown to replicate in trophoblast cell lines, [18][19][20] where HPV infection decreased trophoblast number and trophoblast-endometrial cell adhesion in vitro. 19,20 We investigated for the presence of HPV in the placenta and carried out a histopathological and molecular cross-sectional study of 339 ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

et al. 2015

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“…Juvenile-onset RRP results from transmission in utero or during passage through the birth canal of mothers with active condylomata, yet infections may become symptomatic years later. Recent studies indicate that HPVs can also replicate in trophoblasts and produce infectious particles and that HPVs can be detected in spontaneous aborted tissues (Gomez et al 2008;You et al 2008). Together, these observations add considerable medical significance to HPV infections during pregnancy.…”

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confidence: 97%

Human Papillomavirus Infections: Warts or Cancer?

Chow

Broker

2013

Cold Spring Harbor Perspectives in Biology

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Human papillomaviruses (HPVs) are prevalent pathogens of mucosal and cutaneous epithe-lia. Productive infections of squamous epithelia lead to benign hyperproliferative warts, condylomata, or papillomas. Persistent infections of the anogenital mucosa by high-risk HPV genotypes 16 and 18 and closely related types can infrequently progress to high-grade intraepithelial neoplasias, carcinomas-in-situ, and invasive cancers in women and men. HPV-16 is also associated with a fraction of head and neck cancers. We discuss the interactions of the mucosotropic HPVs with the host regulatory proteins and pathways that lead to benign coexistence and enable HPV DNA amplification or, alternatively, to cancers that no longer support viral production. H uman papillomaviruses (HPVs) are ubiquitous small DNA viruses that comprise a family of more than 150 genotypes. Closely related types show a predilection for particular epithelial tissues and have similar pathogenic properties (de Villiers et al. 2004; Bravo et al. 2010). The mucosotropic HPVs can be sexually transmitted. Infections are frequently asymp-tomatic and are cleared by the immune systems. Active cases are manifested as hyperproliferative lesions but often regress into subclinical persis-tency within a year. Latent infections can reactivate following immunosuppression or upon undergoing repeated cycles of wounding and healing (Fig. 1). A small fraction of persistent infections by the high-risk (HR) HPV genotypes leads to cancers (reviewed by zur Hausen 2009). Worldwide, each year there are about 500,000 new cases of cervical cancer and 275,000 deaths. More than 99% of cervical cancers are caused by high-risk (HR) HPVs, and types 16 and 18 are responsible for about 70% of the cases (Wal-boomers et al. 1999). The HR HPVs are also responsible for a high percentage of cancers of other anogenital sites in men and women. Moreover, HPV-16 is associated with a fraction of the head and neck neoplasias, in particular tonsillar and oro-pharyngeal cancers (reviewed by Syrjänen 2010). In contrast, infections by the low-risk (LR) types 6 and 11 cause 90% of genital warts and essentially all laryngeal papillomas (recurrent respiratory papillomatosis or RRP) (reviewed by Derkay and Wiatrak 2008) but they rarely result in carcinomas. Juvenile-onset RRP results from transmission in utero or during passage through the birth canal of mothers with active condylomata, yet infections may become symptomatic years later. Recent studies

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“…The 3A trophoblast cell line is derived by immortalizing human trophoblasts with a temperature sensitive SV40 T antigen which is inactivated by culturing the cells at 39 ºC during the experiments. This cell line has been reported to support the productive program of HR and LR HPV types (Liu et al, 2005;You et al, 2008). However, viral DNA copy number appears low and decreases with time.…”

Section: A Trophoblastsmentioning

confidence: 82%

Model systems to study the life cycle of human papillomaviruses and HPV-associated cancers

Chow

2015

Virol. Sin.

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The prevalent human papillomaviruses (HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of pRB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.

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Multiple Human Papillomavirus Types Replicate in 3A Trophoblasts

Cited by 55 publications

References 35 publications

A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

Human Papillomavirus Infections: Warts or Cancer?

Model systems to study the life cycle of human papillomaviruses and HPV-associated cancers

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