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
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2021, Current Opinion in VirologyCitation Excerpt :This niche adaptation must have occurred alongside a requirement to maintain productive capability at other, somewhat diverse stratified epithelial sites, including the ectocervix, the lower female genital tract — and particular important for heterosexual transmission, at epithelial sites on the penis. Curiously, high-risk HPV-associated penile cancer is quite rare compared to cervical cancer, which highlights the particular vulnerability of the cervical transformation zone to high-risk HPV oncogenesis [34••,35]. The ectocervix, vagina and vulva, are similarly sites where HPV-associated cancer occurs less often, prompting us to look in finer detail at the regulation of transformation zone of the cervix [34••,36,37], the anus, and indeed other vulnerable epithelial sites (e.g. the tonsillar crypt), where specific epithelial architecture and cellular organisation may facilitate problematic patterns of viral gene expression [6], and/or accentuate the activity of viral gene products.
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2018, Seminars in Colon and Rectal SurgeryCitation Excerpt :There are several mechanisms by which the epithelium may be disrupted, including mechanical trauma6,7 through sexual intercourse, and disruption due to other sexually transmitted infections such as gonorrhea and chlamydia. In people co-infected with HIV, HIV proteins tat and gp120 may also disrupt epithelial tight junctions.7,8 Each of these may therefore be cofactors increasing the risk of initial HPV infection.
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2018, Best Practice and Research: Clinical Obstetrics and GynaecologyCitation Excerpt :HPV is highly transmissible, and although it does not cause clinically recognisable inflammation, it recruits dendritic cells [7,8], T-cells and macrophages and inhibits Langerhans cells [9]. HPV infection also disrupts the mucosal integrity and immunity by down-regulation of antimicrobial [10] and cell adhesion proteins [11]. All these mechanisms and the high prevalence of HPV infection provide a biological basis for a possible increase in HIV transmission ascribed to HPV.
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2017, Seminars in Colon and Rectal SurgeryCitation Excerpt :Intact epithelium has several barriers that typically prevent access of HPV to the basement membrane, including layers of surface keratin, tight junctions between epithelial cells and multiple epithelial layers. There are several mechanisms by which the epithelium may be disrupted, including mechanical trauma6,7 through sexual intercourse, and disruption due to other sexually transmitted infections such as gonorrhea and chlamydia. In people co-infected with HIV, HIV proteins tat and gp120 may also disrupt epithelial tight junctions.7,8
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