Skip to main content
Erschienen in: Archives of Dermatological Research 5/2016

08.04.2016 | Concise Communication

High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?

verfasst von: Alessandro Borghi, Maria D’Accolti, Roberta Rizzo, Annarosa Virgili, Dario Di Luca, Monica Corazza, Elisabetta Caselli

Erschienen in: Archives of Dermatological Research | Ausgabe 5/2016

Einloggen, um Zugang zu erhalten

Abstract

Human herpesvirus 8 (HHV8) has been hypothesized to be a potential cofactor for the development of diverse cutaneous vascular proliferative lesions, including eruptive cherry angiomas. Recent reports evidenced the influence of killer cell immunoglobulin-like receptor (KIR) gene diversity in defining the susceptibility to symptomatic herpesvirus infections. In this study, skin samples from vascular lesions and healthy controls were characterized simultaneously for the presence of HHV8 and for the KIR genotype, focusing upon the presence of the KIR2DL2/DS2 and KIR2DL3 genes, which have been associated to herpesvirus susceptibility. The results showed that about 64 % of the vascular lesions resulted positive for the presence of HHV8, whereas no control healthy skin samples harbored HHV8 DNA. HHV8-positive patients had a significantly increased frequency of KIR2DL2/DS2 homozigosity and a concomitant decrease of the homozygous KIR2DL3 genotype, compared to healthy controls or HHV8-negative patients. Notably, the simultaneous presence of KIR2DL2/DS2 homozygosity and HHV8 infection resulted in a significantly increased risk to develop cutaneous lesions (OR 5.7) compared to the individual factors alone, suggesting that specific KIR genotypes might predispose to HHV8 symptomatic infection, allowing the virus to exert its angioproliferative activity at skin level.
Literatur
1.
Zurück zum Zitat Borghi A, Benedetti S, Corazza M, Gentili V, Ruina G, Di Luca D, Virgili A, Caselli E (2013) Detection of human herpesvirus 8 sequences in cutaneous cherry angiomas. Arch Dermatol Res 305:659–664CrossRefPubMed Borghi A, Benedetti S, Corazza M, Gentili V, Ruina G, Di Luca D, Virgili A, Caselli E (2013) Detection of human herpesvirus 8 sequences in cutaneous cherry angiomas. Arch Dermatol Res 305:659–664CrossRefPubMed
2.
Zurück zum Zitat Borghi A, Caselli E, Di Luca D, Sebastiani A, Perri P, Seraceni S, Contini C, Virgili A (2013) Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report. Infect Agent Cancer 8:41CrossRefPubMedPubMedCentral Borghi A, Caselli E, Di Luca D, Sebastiani A, Perri P, Seraceni S, Contini C, Virgili A (2013) Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary cutaneous anaplastic large-cell lymphoma: a case report. Infect Agent Cancer 8:41CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Brown EE, Whitby D, Vitale F, Fei PC, Del Carpio C, Marshall V, Alberg AJ, Serraino D, Messina A, Gafa L, Goedert JJ (2005) Correlates of human herpesvirus-8 DNA detection among adults in Italy without Kaposi sarcoma. Int J Epidemiol 34:1110–1117CrossRefPubMed Brown EE, Whitby D, Vitale F, Fei PC, Del Carpio C, Marshall V, Alberg AJ, Serraino D, Messina A, Gafa L, Goedert JJ (2005) Correlates of human herpesvirus-8 DNA detection among adults in Italy without Kaposi sarcoma. Int J Epidemiol 34:1110–1117CrossRefPubMed
4.
Zurück zum Zitat Caselli E, Benedetti S, Grigolato J, Caruso A, Di Luca D (2012) Activating transcription factor 4 (ATF4) is upregulated by human herpesvirus 8 infection, increases virus replication and promotes proangiogenic properties. Arch Virol 157:63–74CrossRefPubMed Caselli E, Benedetti S, Grigolato J, Caruso A, Di Luca D (2012) Activating transcription factor 4 (ATF4) is upregulated by human herpesvirus 8 infection, increases virus replication and promotes proangiogenic properties. Arch Virol 157:63–74CrossRefPubMed
5.
Zurück zum Zitat Caselli E, Fiorentini S, Amici C, Di Luca D, Caruso A, Santoro MG (2007) Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-{kappa}B pathway. Blood 109:2718–2726PubMed Caselli E, Fiorentini S, Amici C, Di Luca D, Caruso A, Santoro MG (2007) Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-{kappa}B pathway. Blood 109:2718–2726PubMed
6.
Zurück zum Zitat Caselli E, Rizzo R, Ingianni A, Contini P, Pompei R, Di Luca D (2014) High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus. J Med Virol 86:1745–1751CrossRefPubMed Caselli E, Rizzo R, Ingianni A, Contini P, Pompei R, Di Luca D (2014) High prevalence of HHV8 infection and specific killer cell immunoglobulin-like receptors allotypes in Sardinian patients with type 2 diabetes mellitus. J Med Virol 86:1745–1751CrossRefPubMed
7.
Zurück zum Zitat Cattani P, Cerimele F, Porta D, Graffeo R, Ranno S, Marchetti S, Ricci R, Capodicasa N, Fuga L, Amico R, Cherchi G, Gazzilli M, Zanetti S, Fadda G (2003) Age-specific seroprevalence of human herpesvirus 8 in Mediterranean regions. Clin Microbiol Infect 9:274–279CrossRefPubMed Cattani P, Cerimele F, Porta D, Graffeo R, Ranno S, Marchetti S, Ricci R, Capodicasa N, Fuga L, Amico R, Cherchi G, Gazzilli M, Zanetti S, Fadda G (2003) Age-specific seroprevalence of human herpesvirus 8 in Mediterranean regions. Clin Microbiol Infect 9:274–279CrossRefPubMed
8.
Zurück zum Zitat Cerwenka A, Lanier LL (2001) Natural killer cells, viruses and cancer. Nat Rev Immunol 1:41–49CrossRefPubMed Cerwenka A, Lanier LL (2001) Natural killer cells, viruses and cancer. Nat Rev Immunol 1:41–49CrossRefPubMed
9.
Zurück zum Zitat Cook M, Briggs D, Craddock C, Mahendra P, Milligan D, Fegan C, Darbyshire P, Lawson S, Boxall E, Moss P (2006) Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood 107:1230–1232CrossRefPubMed Cook M, Briggs D, Craddock C, Mahendra P, Milligan D, Fegan C, Darbyshire P, Lawson S, Boxall E, Moss P (2006) Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood 107:1230–1232CrossRefPubMed
10.
Zurück zum Zitat Di Bona D, Scafidi V, Plaia A, Colomba C, Nuzzo D, Occhino C, Tuttolomondo A, Giammanco G, De Grazia S, Montalto G, Duro G, Cippitelli M, Caruso C (2014) HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection. J Infect Dis 210:1083–1089CrossRefPubMed Di Bona D, Scafidi V, Plaia A, Colomba C, Nuzzo D, Occhino C, Tuttolomondo A, Giammanco G, De Grazia S, Montalto G, Duro G, Cippitelli M, Caruso C (2014) HLA and killer cell immunoglobulin-like receptors influence the natural course of CMV infection. J Infect Dis 210:1083–1089CrossRefPubMed
11.
Zurück zum Zitat Estefania E, Gomez-Lozano N, Portero F, de Pablo R, Solis R, Sepulveda S, Vaquero M, Gonzalez MA, Suarez E, Roustan G, Vilches C (2007) Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2. Tissue Antigens 70:34–41CrossRefPubMed Estefania E, Gomez-Lozano N, Portero F, de Pablo R, Solis R, Sepulveda S, Vaquero M, Gonzalez MA, Suarez E, Roustan G, Vilches C (2007) Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2. Tissue Antigens 70:34–41CrossRefPubMed
12.
Zurück zum Zitat Jham BC, Ma T, Hu J, Chaisuparat R, Friedman ER, Pandolfi PP, Schneider A, Sodhi A, Montaner S (2011) Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi’s sarcoma. PLoS One 6:e19103CrossRefPubMedPubMedCentral Jham BC, Ma T, Hu J, Chaisuparat R, Friedman ER, Pandolfi PP, Schneider A, Sodhi A, Montaner S (2011) Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi’s sarcoma. PLoS One 6:e19103CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Jones DC, Peacock S, Hughes D, Traherne JA, Allen RL, Barnardo MC, Friend P, Taylor CJ, Fuggle S, Trowsdale J, Young NT (2014) Killer immunoglobulin-like receptor gene repertoire influences viral load of primary human cytomegalovirus infection in renal transplant patients. Genes Immunol 15:562–568CrossRef Jones DC, Peacock S, Hughes D, Traherne JA, Allen RL, Barnardo MC, Friend P, Taylor CJ, Fuggle S, Trowsdale J, Young NT (2014) Killer immunoglobulin-like receptor gene repertoire influences viral load of primary human cytomegalovirus infection in renal transplant patients. Genes Immunol 15:562–568CrossRef
14.
Zurück zum Zitat Kaplan LD (2013) Human herpesvirus-8: Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma. Hematology Am Soc Hematol Educ Program 2013:103–108PubMed Kaplan LD (2013) Human herpesvirus-8: Kaposi sarcoma, multicentric Castleman disease, and primary effusion lymphoma. Hematology Am Soc Hematol Educ Program 2013:103–108PubMed
16.
Zurück zum Zitat Ma T, Jham BC, Hu J, Friedman ER, Basile JR, Molinolo A, Sodhi A, Montaner S (2010) Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi’s sarcoma. Proc Natl Acad Sci USA 107:14363–14368CrossRefPubMedPubMedCentral Ma T, Jham BC, Hu J, Friedman ER, Basile JR, Molinolo A, Sodhi A, Montaner S (2010) Viral G protein-coupled receptor up-regulates Angiopoietin-like 4 promoting angiogenesis and vascular permeability in Kaposi’s sarcoma. Proc Natl Acad Sci USA 107:14363–14368CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Moesta AK, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P (2008) Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. J Immunol 180:3969–3979CrossRefPubMed Moesta AK, Norman PJ, Yawata M, Yawata N, Gleimer M, Parham P (2008) Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3. J Immunol 180:3969–3979CrossRefPubMed
18.
Zurück zum Zitat Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, Li Y, Ray PE, Gutkind JS (2003) Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3:23–36CrossRefPubMed Montaner S, Sodhi A, Molinolo A, Bugge TH, Sawai ET, He Y, Li Y, Ray PE, Gutkind JS (2003) Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi’s sarcomagenesis and can promote the tumorigenic potential of viral latent genes. Cancer Cell 3:23–36CrossRefPubMed
19.
Zurück zum Zitat Moraru M, Cisneros E, Gomez-Lozano N, de Pablo R, Portero F, Canizares M, Vaquero M, Roustan G, Millan I, Lopez-Botet M, Vilches C (2012) Host genetic factors in susceptibility to herpes simplex type 1 virus infection: contribution of polymorphic genes at the interface of innate and adaptive immunity. J Immunol 188:4412–4420CrossRefPubMed Moraru M, Cisneros E, Gomez-Lozano N, de Pablo R, Portero F, Canizares M, Vaquero M, Roustan G, Millan I, Lopez-Botet M, Vilches C (2012) Host genetic factors in susceptibility to herpes simplex type 1 virus infection: contribution of polymorphic genes at the interface of innate and adaptive immunity. J Immunol 188:4412–4420CrossRefPubMed
20.
Zurück zum Zitat Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223CrossRefPubMed Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, Biassoni R, Moretta L (2001) Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223CrossRefPubMed
21.
Zurück zum Zitat Morris VA, Punjabi AS, Wells RC, Wittkopp CJ, Vart R, Lagunoff M (2012) The KSHV viral IL-6 homolog is sufficient to induce blood to lymphatic endothelial cell differentiation. Virology 428:112–120CrossRefPubMedPubMedCentral Morris VA, Punjabi AS, Wells RC, Wittkopp CJ, Vart R, Lagunoff M (2012) The KSHV viral IL-6 homolog is sufficient to induce blood to lymphatic endothelial cell differentiation. Virology 428:112–120CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Naranatt PP, Krishnan HH, Svojanovsky SR, Bloomer C, Mathur S, Chandran B (2004) Host gene induction and transcriptional reprogramming in Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8)-infected endothelial, fibroblast, and B cells: insights into modulation events early during infection. Cancer Res 64:72–84CrossRefPubMed Naranatt PP, Krishnan HH, Svojanovsky SR, Bloomer C, Mathur S, Chandran B (2004) Host gene induction and transcriptional reprogramming in Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8)-infected endothelial, fibroblast, and B cells: insights into modulation events early during infection. Cancer Res 64:72–84CrossRefPubMed
23.
Zurück zum Zitat Rizzo R, Gentili V, Casetta I, Caselli E, De Gennaro R, Granieri E, Cassai E, Di Luca D, Rotola A (2012) Altered natural killer cells’ response to herpes virus infection in multiple sclerosis involves KIR2DL2 expression. J Neuroimmunol 251:55–64CrossRefPubMed Rizzo R, Gentili V, Casetta I, Caselli E, De Gennaro R, Granieri E, Cassai E, Di Luca D, Rotola A (2012) Altered natural killer cells’ response to herpes virus infection in multiple sclerosis involves KIR2DL2 expression. J Neuroimmunol 251:55–64CrossRefPubMed
24.
Zurück zum Zitat Schulz TF, Cesarman E (2015) Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis. Curr Opin Virol 14:116–128CrossRefPubMed Schulz TF, Cesarman E (2015) Kaposi Sarcoma-associated Herpesvirus: mechanisms of oncogenesis. Curr Opin Virol 14:116–128CrossRefPubMed
25.
Zurück zum Zitat Tanzi E, Zappa A, Caramaschi F, Amendola A, Lasagna D, Gatti L, Ascoli V, Rezza G, Zanetti AR (2005) Human herpesvirus type 8 infection in an area of Northern Italy with high incidence of classical Kaposi’s sarcoma. J Med Virol 76:571–575CrossRefPubMed Tanzi E, Zappa A, Caramaschi F, Amendola A, Lasagna D, Gatti L, Ascoli V, Rezza G, Zanetti AR (2005) Human herpesvirus type 8 infection in an area of Northern Italy with high incidence of classical Kaposi’s sarcoma. J Med Virol 76:571–575CrossRefPubMed
26.
Zurück zum Zitat Winter CC, Gumperz JE, Parham P, Long EO, Wagtmann N (1998) Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. J Immunol 161:571–577PubMed Winter CC, Gumperz JE, Parham P, Long EO, Wagtmann N (1998) Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition. J Immunol 161:571–577PubMed
Metadaten
Titel
High prevalence of specific KIR types in patients with HHV-8 positive cutaneous vascular lesions: a possible predisposing factor?
verfasst von
Alessandro Borghi
Maria D’Accolti
Roberta Rizzo
Annarosa Virgili
Dario Di Luca
Monica Corazza
Elisabetta Caselli
Publikationsdatum
08.04.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Dermatological Research / Ausgabe 5/2016
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-016-1643-x

Weitere Artikel der Ausgabe 5/2016

Archives of Dermatological Research 5/2016 Zur Ausgabe

Leitlinien kompakt für die Dermatologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Dermatologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.