Trends in Microbiology
OpinionMucosal junctions: open doors to HPV and HIV infections?
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)
Epithelial metaplasia: adult stem cell reprogramming and (pre)neoplastic transformation mediated by inflammation?
Trends Mol. Med.
(2009)Classification of papillomaviruses
Virology
(2004)Transforming growth factor-beta1-mediated slug and snail transcription factor up-regulation reduces the density of Langerhans cells in epithelial metaplasia by affecting E-cadherin expression
Am. J. Pathol.
(2008)- et al.
‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments
Curr. Opin. Cell Biol.
(2002) - et al.
Keratin function in skin epithelia: a broadening palette with surprising shades
Curr. Opin. Cell Biol.
(2007) High intraepithelial expression of estrogen and progesterone receptors in the transformation zone of the uterine cervix
Am. J. Obstet. Gynecol.
(2003)17 Beta-estradiol (E2) plus tumor necrosis factor-alpha induces a distorted maturation of human monocyte-derived dendritic cells and promotes their capacity to initiate T-helper 2 responses
Hum. Immunol.
(2008)Cytokines and Langerhans cell mobilisation in mouse and man
Cytokine
(2005)Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells
Blood
(1999)Colposcopic appearance of anal squamous intraepithelial lesions: relationship to histopathology
Dis. Colon Rectum
(1997)