Trends in Microbiology
Volume 19, Issue 3, March 2011, Pages 114-120
Journal home page for Trends in Microbiology

Opinion
Mucosal junctions: open doors to HPV and HIV infections?

https://doi.org/10.1016/j.tim.2010.12.006Get rights and content

Throughout adult life, new developmental commitment of adult stem cells causes reversible epithelial replacements in various mucosal surfaces, including the uterine cervix and the anal canal. Located at the squamocolumnar junctions, these metaplastic conversions are associated with chronic inflammation and deregulated expression of soluble and cell-membrane factors important for antiviral immune response. In this paper, we propose that these histological and immunological features increase the susceptibility of these metaplastic microenvironments to human papillomavirus and human immunodeficiency virus infections. Identification of the anatomical sites and cell populations within the anogenital tract, which is the site primary infected by these viruses, is crucial for the understanding of the pathogenesis of viral disease and development of antiviral strategies.

Section snippets

Metaplastic cells and sexually transmitted viruses

The cervical and anal transformation or transition zones (TZs) are dynamic areas of a few millimeters in size, in which a columnar glandular epithelium coexists with a squamous epithelium, and result from an adaptive process called metaplasia 1, 2 (Figure 1). These metaplastic conversions are influenced respectively by the acidification of vaginal pH and by trauma such as that resulting from receptive anal intercourse, and can be considered as a stepwise progression of changes.

In the first

Mucosal junctions and HPV infection

Transmitted predominantly through direct contact, HPVs are epitheliotropic viruses that cause hyperproliferative lesions of the cutaneous and mucosal epithelia. To date, more than 100 HPV genotypes have been fully characterized based on the isolation of complete genomes, and about one-third specifically infect the anogenital mucosal surfaces [13]. The annual prevalence of infections with genital HPV is about 30% in young adults during the years after beginning sexual activity, and some HPV

Mucosal junctions and HIV infection

HIV 1 and 2 are transmitted by sexual contact, through blood, or from mother to child, and are clinically indistinguishable in causing acquired immunodeficiency syndrome (AIDS), a condition characterized by the appearance of opportunistic infections due to the deterioration of the immune system [35]. At the end of 2008, the number of adults and children living with HIV/AIDS was estimated by the World Health Organization and Joint United Nations Programme on HIV/AIDS to have reached 33 million

Mucosal junctions and antiviral protections

HPV and HIV infections are dependent on successful transport to susceptible target cells and on survival of the virus and/or infected cells in mucosal surfaces and secretions. Both cellular responses and secretion of innate soluble factors are involved in antiviral defense, and there is accumulating evidence that both are altered in anal and cervical squamocolumnar junctions.

The anogenital mucosa is composed not only of epithelial cells but also of a type of immature antigen-presenting cells,

Positive interactions between HPV and HIV infections

One of the consequences of similar preferential infection sites for both HPV and HIV is that these viruses could have the opportunity to cooperate. Consistent with this, recent studies suggested that HPV increases the risk of HIV infection 11, 12. As mentioned above, a potential explanation could be the decreased production of antimicrobial molecules by HPV-infected keratinocytes 67, 70. Moreover, the HPV16 E7 oncoprotein has the ability to reduce E-cadherin expression [71] and could indirectly

Concluding remarks

Although the exact cellular and molecular events involved in initial HPV and HIV infection and transmission are still unclear, the peculiar microenvironment of squamocolumnar junctions might promote the successful transport of these viruses across the mucosal barrier to susceptible target cells. We support the notion that the altered pattern of soluble factors observed in anal and cervical TZs could prevent the local immune system from establishing efficient antiviral immunity against viral

Acknowledgments

We thank Jacques Boniver and Christelle Meuris for helpful discussions. M. Herfs is Postdoctoral Researcher of the Belgian National Fund for Scientific Research. The authors declare that they have no conflicts of interest.

Glossary

Cytokines
small signalling proteins produced and secreted by individual cells, which transmit distinct messages of activation, inhibition, chemoattraction or apoptosis to other cells. The term ‘cytokine’ encompasses interleukins, chemokines, interferons, tumor necrosis factors and transforming growth factors.
Chemokines
small cytokines whose name is derived from their ability to induce directed chemotaxis in nearby responsive cells.
Defensins
small (4–6 kDa) cationic peptides with high antimicrobial

References (75)

  • P. Mukonoweshuro

    Audit of the histological definition of cervical transformation zone

    J. Clin. Pathol.

    (2005)
  • J.M. Slack

    Metaplasia and transdifferentiation: from pure biology to the clinic

    Nat. Rev. Mol. Cell Biol.

    (2007)
  • A.T. Haase

    Targeting early infection to prevent HIV-1 mucosal transmission

    Nature

    (2010)
  • M. Sapp et al.

    Viral entry mechanisms: human papillomavirus and a long journey from extracellular matrix to the nucleus

    FEBS J.

    (2009)
  • R.J. Shattock et al.

    Inhibiting sexual transmission of HIV-1 infection

    Nat. Rev. Microbiol.

    (2003)
  • L. Abramowitz

    Anal squamous intraepithelial lesions and condyloma in HIV-infected heterosexual men, homosexual men and women: prevalence and associated factors

    AIDS

    (2007)
  • A. Damay

    Human papillomavirus (HPV) prevalence and type distribution, and HPV-associated cytological abnormalities in anal specimens from men infected with HIV who have sex with men

    J. Med. Virol.

    (2010)
  • M. Frisch

    Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome

    J. Natl. Cancer Inst.

    (2000)
  • B. Auvert

    Association of oncogenic and nononcogenic human papillomavirus with HIV incidence

    J. Acquir. Immune Defic. Syndr.

    (2010)
  • K.K. Smith-McCune

    Type-specific cervico-vaginal human papillomavirus infection increases risk of HIV acquisition independent of other sexually transmitted infections

    PLoS One

    (2010)
  • R. Ghittoni

    The biological properties of E6 and E7 oncoproteins from human papillomaviruses

    Virus Genes

    (2010)
  • J. Bodily et al.

    Persistence of human papillomavirus infection: keys to malignant progression

    Trends Microbiol.

    (2010)
  • E. Burghardt et al.

    Site and origin of squamous cervical cancer: a histomorphologic study

    Obstet. Gynecol.

    (1983)
  • C.B. Woodman

    The natural history of cervical HPV infection: unresolved issues

    Nat. Rev. Cancer

    (2007)
  • R.C. Kines

    The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding

    Proc. Natl. Acad. Sci. U.S.A.

    (2009)
  • P. Maddox

    Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma

    J. Clin. Pathol.

    (1999)
  • J.N. Roberts

    Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan

    Nat. Med.

    (2007)
  • D.V. Kazakov

    Adenosis tumor of anogenital mammary-like glands: a case report and demonstration of clonality by HUMARA assay

    J. Cutan. Pathol.

    (2006)
  • K. Gejima

    Expression of estrogen receptor-alpha protein in the rat digestive tract

    In Vivo

    (2007)
  • D.A. Elson

    Sensitivity of the cervical transformation zone to estrogen-induced squamous carcinogenesis

    Cancer Res.

    (2000)
  • C.H. Buckley

    The pathology of intra-uterine contraceptive devices

    Curr. Top. Pathol.

    (1994)
  • F. Yuan

    Altered growth and viral gene expression in human papillomavirus type 16-containing cancer cell lines treated with progesterone

    Cancer Invest.

    (1999)
  • D. Bhattacharya

    Oestrogen increases S-phase fraction and oestrogen and progesterone receptors in human cervical cancer in vivo

    Br. J. Cancer

    (1997)
  • C.R. Wira

    Antigen-presenting cells in the female reproductive tract: influence of estradiol on antigen presentation by vaginal cells

    Endocrinology

    (2000)
  • M.B. Graham

    Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection

    J. Exp. Med.

    (1994)
  • M. Kobayashi

    A pathogenic role of Th2 cells and their cytokine products on the pulmonary metastasis of murine B16 melanoma

    J. Immunol.

    (1998)
  • L.O. Kallings

    The first postmodern pandemic: 25 years of HIV/AIDS

    J. Intern. Med.

    (2008)
  • Cited by (0)

    View full text