Interaction of human papillomavirus type 16 and adeno-associated virus type 2 co-infecting human cervical epithelium.

Walz, Christian M.; Deprez, A; Dupressoir, Thierry; D√orst, M; Rabreau, Michèle; Schlehofer, Joerg R.

doi:10.1099/0022-1317-78-6-1441

Cited by 90 publications

(88 citation statements)

References 53 publications

(35 reference statements)

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“…Previous studies in different countries (France, Germany, Italy, United States) have found a high prevalence of AAV DNA (up to 70%) using PCR techniques on cervical tissues from nondiseased women and among women with cervical dyplasia. 13,26,27 Friedman-Einat et al did not find AAV-2 DNA among HPV-positive biopsy specimens in 21 Israeli women and observed an 18% AAV-2 DNA positivity in 61 women with suspected HSV-2 infection. 62 In addition to PCR studies, AAV DNA has been detected in cervical epithelium using in situ hybridization, 27 and infectious AAV virions have been isolated from the genital area.…”

Section: Discussionmentioning

confidence: 96%

“…13,26,27 Friedman-Einat et al did not find AAV-2 DNA among HPV-positive biopsy specimens in 21 Israeli women and observed an 18% AAV-2 DNA positivity in 61 women with suspected HSV-2 infection. 62 In addition to PCR studies, AAV DNA has been detected in cervical epithelium using in situ hybridization, 27 and infectious AAV virions have been isolated from the genital area. 12,63 However, Southern blot studies of AAV PCR positive biopsy specimens have found that viral AAV DNA was rarely detectable, 13,27 indicating low copy numbers of AAV in these infected cells.…”

Section: Discussionmentioning

confidence: 96%

“…62 In addition to PCR studies, AAV DNA has been detected in cervical epithelium using in situ hybridization, 27 and infectious AAV virions have been isolated from the genital area. 12,63 However, Southern blot studies of AAV PCR positive biopsy specimens have found that viral AAV DNA was rarely detectable, 13,27 indicating low copy numbers of AAV in these infected cells. In contrast, Strickler et al 42 found no AAV DNA in the genital tract of 291 Jamaican women and 79 US university students using AAV cap and rep gene primers.…”

Section: Discussionmentioning

confidence: 99%

“…67 Furthermore, previous studies suggest that coinfection with AAV and HPV may induce cytopathic effects, preventing the respective cells from surviving. 27 Alternatively, AAV may reduce the chance of malignant conversion of HPVinfected cells by downregulating E6/E7. 27,35 These findings of an association between AAV and invasive cancer are intriguing and provide some support for the hypothesis that an interaction between AAV and HPV may exist.…”

Section: Discussionmentioning

confidence: 99%

“…Laboratory data indicate that helper viruses of AAV include adenovirus, herpes simplex virus, cytomegalovirus, Epstein-Barr virus (EBV), human herpesvirus 6, vaccinia virus and HPV. 6,[21][22][23][24][25][26][27] In vitro data indicate that without its helper virus, AAV may become latent by inserting their DNA site-specifically into the host cell chromosome and may later be reactivated after infection with their helper virus. 28 The recent detection of AAV in human amnion fluids 12 in the absence of helper viruses, however, indicates the possibility of helper-independent replication in appropriate tissues.…”

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confidence: 99%

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Adeno‐associated virus seropositivity and HPV‐induced cervical cancer in Spain and Colombia

et al. 2001

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Extensive experimental and limited epidemiologic data suggest that adeno-associated viruses (AAV) can have antioncogenic activity and may be protective factors for the development of cervical cancer. To examine the association between AAV-2 IgG antibodies and cervical neoplasia in Spain and Colombia, we tested for AAV-2 antibodies using an ELISA assay for 109 women with invasive cervical cancer, 100 population-based controls age-matched to the invasive cases, 77 women with carcinoma in situ (CIN III) and 100 clinicbased controls age-matched to the CIN III cases. Human papillomavirus (HPV) DNA was detected in cervical exfoliated cells by polymerase chain reaction using HPV-L1 and GP5؉/6؉ consensus primers. The prevalence of AAV-2 antibody titers >100 was significantly lower in invasive cervical cancer cases than control participants. When comparing women with invasive cancer with controls or with CIN III cases, a pattern of decreasing cervical cancer risk with increasing AAV-2 titers was observed. Elevated AAV antibody titers (>100) were inversely associated with invasive cervical cancer (OR 0.3; 95% CI 0.1-0.7), although results were not statistically significant after controlling for HPV (OR 0.4; 95% CI 0.1-1.6). In contrast, AAV-2 antibodies were not significantly associated with the risk of CIN III (OR 1.4; 95% CI 0.3-6.8). These results provide supportive evidence that AAV infection may be a protective factor for the development of invasive cervical cancer. Alternatively, the lower AAV-2 seroprevalence in invasive cervical cancer cases may be due to an immunosuppressive effect of cervical cancer on AAV antibody response. To investigate whether a direct viral interaction is occurring, future studies should aim to resolve at what frequency AAV is found in the genital tract and to clarify further whether AAV may infect the same HPV-positive cells in the cervix.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Adeno‐associated virus seropositivity and HPV‐induced cervical cancer in Spain and Colombia

et al. 2001

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Adeno-associated virus and development of cervical neoplasia

et al. 1999

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Evidence from several sources has suggested that adeno-associated virus (AAV) infection might protect against cervical cancer, in part, by interfering with human papillomavirus (HPV)-induced tumorigenesis. Detection of AAV type 2 (AAV-2) DNA in cervical tissues has been reported. However, there have been few in vivo studies of women with cervical HPV infection or neoplasia, and these have reported inconsistent results. Therefore, we used polymerase chain reaction (PCR) assays targeted to the AAV-2 rep and cap genes to test tissue specimens from women in an epidemiological study of cervical neoplasia in Jamaica. We tested 105 women with low-grade cervical intraepithelial neoplasia (CIN-1), 92 women with CIN-3/carcinoma in situ or invasive cancer (CIN-3/CA), and 94 normal subjects. PCR amplification of human beta-globin DNA was found in almost all cervical specimens, indicating that these materials were adequate for PCR testing. The prevalence of HPV DNA, determined by HPV L1 consensus primer PCR was, as expected, strongly associated with presence and grade of neoplasia. Each of the AAV PCR assays detected as few as 10 copies of the virus genome. However, none of the 291 cervical specimens from Jamaican subjects tested positive for AAV DNA. Negative AAV PCR results were also obtained in tests of cervical samples from 79 university students in the United States. Exposure to AAV was assessed further by serology. Using a whole virus AAV-2 sandwich enzyme-linked immunosorbent assay, we found no relationship between AAV antibodies and presence or grade of neoplasia in either the Jamaican study subjects or women enrolled in a U.S. cervical cancer case (n = 74) -control (n = 77) study. Overall, the data provide no evidence that AAV infection plays a role in cervical tumorigenesis or that AAV commonly infects cervical epithelial cells.

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Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV)

Erles¹,

Sebökovà²,

Schlehofer³

1999

J. Med. Virol.

307

214

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In view of presumed non-pathogenicity, tumor suppressive properties, and site-specific integration of the viral genome the human parvovirus, adeno-associated virus (AAV) has gained great interest as a gene transduction vector. Data on the seroprevalence of antibodies to AAV vary between reports, probably due to the different serological methods used. In order to understand better the immune response to AAV during natural infection, sera from different age groups and various geographical regions were compared for AAV antibodies using an ELISA. The data show that the prevalence of antibodies to AAV is similar in Europe (Germany, France, and Switzerland), Brazil, and Japan, indicating worldwide infection. It was confirmed that infection takes place during childhood. However, declining seropositivity thereafter and a second increase of seropositivity after 30 years of age suggests reinfection or reactivation of latent virus in particular as the prevalence of IgM antibodies in adults is relatively high. Furthermore, pregnant women were found to be significantly more frequently seropositive than non-pregnant controls, hinting at a reactivation of persistent AAV (up to 80% of women carry AAV in genital tissue) in specific hormonal conditions, e.g., pregnancy. Cross-reaction of serum antibodies with the different AAV types (defined by complement fixation) was observed by ELISA and neutralization tests confirming earlier results. The results suggest an unstable AAV antibody response allowing lifelong reinfection or reactivation of persisting virus possibly due to partial immunotolerance after an infection in utero, at delivery or during early infancy.

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Interaction of human papillomavirus type 16 and adeno-associated virus type 2 co-infecting human cervical epithelium.

Cited by 90 publications

References 53 publications

Adeno‐associated virus seropositivity and HPV‐induced cervical cancer in Spain and Colombia

Adeno‐associated virus seropositivity and HPV‐induced cervical cancer in Spain and Colombia

Adeno-associated virus and development of cervical neoplasia

Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV)

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