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Published in: Journal of NeuroVirology 3/2017

Open Access 01-06-2017

Distribution of cellular HSV-1 receptor expression in human brain

Authors: Richard Lathe, Juergen G. Haas

Published in: Journal of NeuroVirology | Issue 3/2017

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Abstract

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.
Literature
go back to reference Baringer JR, Swoveland P (1973) Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med 288:648–650CrossRefPubMed Baringer JR, Swoveland P (1973) Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med 288:648–650CrossRefPubMed
go back to reference Campadelli-Fiume G, Menotti L, Avitabile E, Gianni T (2012a) Viral and cellular contributions to herpes simplex virus entry into the cell. Curr Opin Virol 2:28–36CrossRefPubMed Campadelli-Fiume G, Menotti L, Avitabile E, Gianni T (2012a) Viral and cellular contributions to herpes simplex virus entry into the cell. Curr Opin Virol 2:28–36CrossRefPubMed
go back to reference Caracausi M, Rigon V, Piovesan A, Strippoli P, Vitale L, Pelleri MC (2016) A quantitative transcriptome reference map of the normal human hippocampus. Hippocampus 26:13–26CrossRefPubMed Caracausi M, Rigon V, Piovesan A, Strippoli P, Vitale L, Pelleri MC (2016) A quantitative transcriptome reference map of the normal human hippocampus. Hippocampus 26:13–26CrossRefPubMed
go back to reference Cheshenko N, Trepanier JB, Segarra TJ, Fuller AO, Herold BC (2010) HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: novel prevention target. PLoS One 5:e11829CrossRefPubMedPubMedCentral Cheshenko N, Trepanier JB, Segarra TJ, Fuller AO, Herold BC (2010) HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: novel prevention target. PLoS One 5:e11829CrossRefPubMedPubMedCentral
go back to reference Croen KD, Ostrove JM, Dragovic LJ, Smialek JE, Straus SE (1987) Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene “anti-sense” transcript by in situ hybridization. N Engl J Med 317:1427–1432CrossRefPubMed Croen KD, Ostrove JM, Dragovic LJ, Smialek JE, Straus SE (1987) Latent herpes simplex virus in human trigeminal ganglia. Detection of an immediate early gene “anti-sense” transcript by in situ hybridization. N Engl J Med 317:1427–1432CrossRefPubMed
go back to reference Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jaaskelainen AJ, Smura T, Rosenberg A, Hill DA, DeBiasi RL, Vezina G, Timofeev J, Rodriguez FJ, Levanov L, Razak J, Iyengar P, Hennenfent A, Kennedy R, Lanciotti R, du Plessis A, Vapalahti O (2016) Zika cirus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 374:2142–2151CrossRefPubMed Driggers RW, Ho CY, Korhonen EM, Kuivanen S, Jaaskelainen AJ, Smura T, Rosenberg A, Hill DA, DeBiasi RL, Vezina G, Timofeev J, Rodriguez FJ, Levanov L, Razak J, Iyengar P, Hennenfent A, Kennedy R, Lanciotti R, du Plessis A, Vapalahti O (2016) Zika cirus infection with prolonged maternal viremia and fetal brain abnormalities. N Engl J Med 374:2142–2151CrossRefPubMed
go back to reference Dypvik AT, Bland BH (2004) Functional connectivity between the red nucleus and the hippocampus supports the role of hippocampal formation in sensorimotor integration. J Neurophysiol 92:2040–2050CrossRefPubMed Dypvik AT, Bland BH (2004) Functional connectivity between the red nucleus and the hippocampus supports the role of hippocampal formation in sensorimotor integration. J Neurophysiol 92:2040–2050CrossRefPubMed
go back to reference Esiri MM (1982) Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J Neurol Sci 54:209–226CrossRefPubMed Esiri MM (1982) Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J Neurol Sci 54:209–226CrossRefPubMed
go back to reference Furuta Y, Takasu T, Sato KC, Fukuda S, Inuyama Y, Nagashima K (1992) Latent herpes simplex virus type 1 in human geniculate ganglia. Acta Neuropathol 84:39–44CrossRefPubMed Furuta Y, Takasu T, Sato KC, Fukuda S, Inuyama Y, Nagashima K (1992) Latent herpes simplex virus type 1 in human geniculate ganglia. Acta Neuropathol 84:39–44CrossRefPubMed
go back to reference Geraghty RJ, Krummenacher C, Cohen GH, Eisenberg RJ, Spear PG (1998) Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280:1618–1620CrossRefPubMed Geraghty RJ, Krummenacher C, Cohen GH, Eisenberg RJ, Spear PG (1998) Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280:1618–1620CrossRefPubMed
go back to reference Gilden DH, Mahalingam R, Cohrs RJ, Tyler KL (2007) Herpesvirus infections of the nervous system. Nat Clin Pract Neurol 3:82–94CrossRefPubMed Gilden DH, Mahalingam R, Cohrs RJ, Tyler KL (2007) Herpesvirus infections of the nervous system. Nat Clin Pract Neurol 3:82–94CrossRefPubMed
go back to reference Guillemette-Artur P, Besnard M, Eyrolle-Guignot D, Jouannic JM, Garel C (2016) Prenatal brain MRI of fetuses with Zika virus infection. Pediatr Radiol 46:1032–1039CrossRefPubMed Guillemette-Artur P, Besnard M, Eyrolle-Guignot D, Jouannic JM, Garel C (2016) Prenatal brain MRI of fetuses with Zika virus infection. Pediatr Radiol 46:1032–1039CrossRefPubMed
go back to reference Guzman G, Oh S, Shukla D, Engelhard HH, Valyi-Nagy T (2006) Expression of entry receptor nectin-1 of herpes simplex virus 1 and/or herpes simplex virus 2 in normal and neoplastic human nervous system tissues. Acta Virol 50:59–66PubMed Guzman G, Oh S, Shukla D, Engelhard HH, Valyi-Nagy T (2006) Expression of entry receptor nectin-1 of herpes simplex virus 1 and/or herpes simplex virus 2 in normal and neoplastic human nervous system tissues. Acta Virol 50:59–66PubMed
go back to reference Harberts E, Yao K, Wohler JE, Maric D, Ohayon J, Henkin R, Jacobson S (2011) Human herpesvirus-6 entry into the central nervous system through the olfactory pathway. Proc Natl Acad Sci U S A 108:13734–13739CrossRefPubMedPubMedCentral Harberts E, Yao K, Wohler JE, Maric D, Ohayon J, Henkin R, Jacobson S (2011) Human herpesvirus-6 entry into the central nervous system through the olfactory pathway. Proc Natl Acad Sci U S A 108:13734–13739CrossRefPubMedPubMedCentral
go back to reference Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL, Abajian C, Beckmann CF, Bernard A, Bertagnolli D, Boe AF, Cartagena PM, Chakravarty MM, Chapin M, Chong J, Dalley RA, Daly BD, Dang C, Datta S, Dee N, Dolbeare TA, Faber V, Feng D, Fowler DR, Goldy J, Gregor BW, Haradon Z, Haynor DR, Hohmann JG, Horvath S, Howard RE, Jeromin A, Jochim JM, Kinnunen M, Lau C, Lazarz ET, Lee C, Lemon TA, Li L, Li Y, Morris JA, Overly CC, Parker PD, Parry SE, Reding M, Royall JJ, Schulkin J, Sequeira PA, Slaughterbeck CR, Smith SC, Sodt AJ, Sunkin SM, Swanson BE, Vawter MP, Williams D, Wohnoutka P, Zielke HR, Geschwind DH, Hof PR, Smith SM, Koch C, Grant SG, Jones AR (2012) An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489:391–399CrossRefPubMedPubMedCentral Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, van de Lagemaat LN, Smith KA, Ebbert A, Riley ZL, Abajian C, Beckmann CF, Bernard A, Bertagnolli D, Boe AF, Cartagena PM, Chakravarty MM, Chapin M, Chong J, Dalley RA, Daly BD, Dang C, Datta S, Dee N, Dolbeare TA, Faber V, Feng D, Fowler DR, Goldy J, Gregor BW, Haradon Z, Haynor DR, Hohmann JG, Horvath S, Howard RE, Jeromin A, Jochim JM, Kinnunen M, Lau C, Lazarz ET, Lee C, Lemon TA, Li L, Li Y, Morris JA, Overly CC, Parker PD, Parry SE, Reding M, Royall JJ, Schulkin J, Sequeira PA, Slaughterbeck CR, Smith SC, Sodt AJ, Sunkin SM, Swanson BE, Vawter MP, Williams D, Wohnoutka P, Zielke HR, Geschwind DH, Hof PR, Smith SM, Koch C, Grant SG, Jones AR (2012) An anatomically comprehensive atlas of the adult human brain transcriptome. Nature 489:391–399CrossRefPubMedPubMedCentral
go back to reference Hondius DC, van Nierop P, Li KW, Hoozemans JJ, van der Schors RC, van Haastert ES, van der Vies SM, Rozemuller AJ, Smit AB (2016) Profiling the human hippocampal proteome at all pathologic stages of Alzheimer’s disease. Alzheimers Dement 12:654–668CrossRefPubMed Hondius DC, van Nierop P, Li KW, Hoozemans JJ, van der Schors RC, van Haastert ES, van der Vies SM, Rozemuller AJ, Smit AB (2016) Profiling the human hippocampal proteome at all pathologic stages of Alzheimer’s disease. Alzheimers Dement 12:654–668CrossRefPubMed
go back to reference Horvath S, Prandovszky E, Kis Z, Krummenacher C, Eisenberg RJ, Cohen GH, Janka Z, Toldi J (2006) Spatiotemporal changes of the herpes simplex virus entry receptor nectin-1 in murine brain during postnatal development. J. Neurovirol. 12:161–170CrossRefPubMed Horvath S, Prandovszky E, Kis Z, Krummenacher C, Eisenberg RJ, Cohen GH, Janka Z, Toldi J (2006) Spatiotemporal changes of the herpes simplex virus entry receptor nectin-1 in murine brain during postnatal development. J. Neurovirol. 12:161–170CrossRefPubMed
go back to reference Johnson MB, Kawasawa YI, Mason CE, Krsnik Z, Coppola G, Bogdanovic D, Geschwind DH, Mane SM, State MW, Sestan N (2009) Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62:494–509CrossRefPubMedPubMedCentral Johnson MB, Kawasawa YI, Mason CE, Krsnik Z, Coppola G, Bogdanovic D, Geschwind DH, Mane SM, State MW, Sestan N (2009) Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 62:494–509CrossRefPubMedPubMedCentral
go back to reference Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, Sousa AM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Sestan N (2011) Spatio-temporal transcriptome of the human brain. Nature 478:483–489CrossRefPubMedPubMedCentral Kang HJ, Kawasawa YI, Cheng F, Zhu Y, Xu X, Li M, Sousa AM, Pletikos M, Meyer KA, Sedmak G, Guennel T, Shin Y, Johnson MB, Krsnik Z, Mayer S, Fertuzinhos S, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Sestan N (2011) Spatio-temporal transcriptome of the human brain. Nature 478:483–489CrossRefPubMedPubMedCentral
go back to reference Kleinschmidt-DeMasters BK, Gilden DH (2001) The expanding spectrum of herpesvirus infections of the nervous system. Brain Pathol 11:440–451CrossRefPubMed Kleinschmidt-DeMasters BK, Gilden DH (2001) The expanding spectrum of herpesvirus infections of the nervous system. Brain Pathol 11:440–451CrossRefPubMed
go back to reference Kopp SJ, Banisadr G, Glajch K, Maurer UE, Grunewald K, Miller RJ, Osten P, Spear PG (2009) Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1. Proc Natl Acad Sci U S A 106:17916–17920CrossRefPubMedPubMedCentral Kopp SJ, Banisadr G, Glajch K, Maurer UE, Grunewald K, Miller RJ, Osten P, Spear PG (2009) Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1. Proc Natl Acad Sci U S A 106:17916–17920CrossRefPubMedPubMedCentral
go back to reference Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf KR, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Yuan XF, Zhang B, Zwingman TA, Jones AR (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168–176CrossRefPubMed Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf KR, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Yuan XF, Zhang B, Zwingman TA, Jones AR (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445:168–176CrossRefPubMed
go back to reference Livorsi D, Anderson E, Qureshi S, Howard M, Wang YF, Franco-Paredes C (2010) Brainstem encephalitis: an unusual presentation of herpes simplex virus infection. J Neurol 257:1432–1437CrossRefPubMed Livorsi D, Anderson E, Qureshi S, Howard M, Wang YF, Franco-Paredes C (2010) Brainstem encephalitis: an unusual presentation of herpes simplex virus infection. J Neurol 257:1432–1437CrossRefPubMed
go back to reference McCarthy FP, Giles ML, Rowlands S, Purcell KJ, Jones CA (2011) Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Cochrane Database Syst Rev CD008371 McCarthy FP, Giles ML, Rowlands S, Purcell KJ, Jones CA (2011) Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Cochrane Database Syst Rev CD008371
go back to reference McFarland DJ, Hotchin J (1987) Contrasting patterns of virus spread and neuropathology following microinjection of herpes simplex virus into the hippocampus or cerebellum of mice. J Neurol Sci 79:255–265CrossRefPubMed McFarland DJ, Hotchin J (1987) Contrasting patterns of virus spread and neuropathology following microinjection of herpes simplex virus into the hippocampus or cerebellum of mice. J Neurol Sci 79:255–265CrossRefPubMed
go back to reference Mori I, Nishiyama Y, Yokochi T, Kimura Y (2005) Olfactory transmission of neurotropic viruses. J. Neurovirol. 11:129–137CrossRefPubMed Mori I, Nishiyama Y, Yokochi T, Kimura Y (2005) Olfactory transmission of neurotropic viruses. J. Neurovirol. 11:129–137CrossRefPubMed
go back to reference Nioche C, Cabanis EA, Habas C (2009) Functional connectivity of the human red nucleus in the brain resting state at 3T. Am J Neuroradiol 30:396–403CrossRefPubMed Nioche C, Cabanis EA, Habas C (2009) Functional connectivity of the human red nucleus in the brain resting state at 3T. Am J Neuroradiol 30:396–403CrossRefPubMed
go back to reference Perez A, Li QX, Perez-Romero P, Delassus G, Lopez SR, Sutter S, McLaren N, Fuller AO (2005) A new class of receptor for herpes simplex virus has heptad repeat motifs that are common to membrane fusion proteins. J Virol 79:7419–7430CrossRefPubMedPubMedCentral Perez A, Li QX, Perez-Romero P, Delassus G, Lopez SR, Sutter S, McLaren N, Fuller AO (2005) A new class of receptor for herpes simplex virus has heptad repeat motifs that are common to membrane fusion proteins. J Virol 79:7419–7430CrossRefPubMedPubMedCentral
go back to reference Prandovszky E, Horvath S, Gellert L, Kovacs SK, Janka Z, Toldi J, Shukla D, Valyi-Nagy T (2008) Nectin-1 (HveC) is expressed at high levels in neural subtypes that regulate radial migration of cortical and cerebellar neurons of the developing human and murine brain. J Neurovirol 14:164–172CrossRefPubMed Prandovszky E, Horvath S, Gellert L, Kovacs SK, Janka Z, Toldi J, Shukla D, Valyi-Nagy T (2008) Nectin-1 (HveC) is expressed at high levels in neural subtypes that regulate radial migration of cortical and cerebellar neurons of the developing human and murine brain. J Neurovirol 14:164–172CrossRefPubMed
go back to reference Taylor JM, Lin E, Susmarski N, Yoon M, Zago A, Ware CF, Pfeffer K, Miyoshi J, Takai Y, Spear PG (2007) Alternative entry receptors for herpes simplex virus and their roles in disease. Cell Host Microbe 2:19–28CrossRefPubMedPubMedCentral Taylor JM, Lin E, Susmarski N, Yoon M, Zago A, Ware CF, Pfeffer K, Miyoshi J, Takai Y, Spear PG (2007) Alternative entry receptors for herpes simplex virus and their roles in disease. Cell Host Microbe 2:19–28CrossRefPubMedPubMedCentral
go back to reference Theil D, Arbusow V, Derfuss T, Strupp M, Pfeiffer M, Mascolo A, Brandt T (2001) Prevalence of HSV-1 LAT in human trigeminal, geniculate, and vestibular ganglia and its implication for cranial nerve syndromes. Brain Pathol 11:408–413CrossRefPubMed Theil D, Arbusow V, Derfuss T, Strupp M, Pfeiffer M, Mascolo A, Brandt T (2001) Prevalence of HSV-1 LAT in human trigeminal, geniculate, and vestibular ganglia and its implication for cranial nerve syndromes. Brain Pathol 11:408–413CrossRefPubMed
Metadata
Title
Distribution of cellular HSV-1 receptor expression in human brain
Authors
Richard Lathe
Juergen G. Haas
Publication date
01-06-2017
Publisher
Springer International Publishing
Published in
Journal of NeuroVirology / Issue 3/2017
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-016-0504-x

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