Experimental oral herpes simplex Virus-1 (HSV-1) co-infection in Simian Immunodeficiency Virus (SIV)-infected rhesus macaques

Meropi Aravantinou, Olga Mizenina, Giulia Calenda, Jessica Kenney, Ines Frank, Jeffrey D. Lifson, Moriah Szpara, Lichen Jing, David M. Koelle, Natalia Teleshova, Brooke Grasperge, James Blanchard, Agegnehu Gettie, Elena Martinelli, Nina Derby

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Abstract

Herpes simplex virus 1 and 2 (HSV-1/2) similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV) transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP) models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

Original languageEnglish (US)
Article number2342
JournalFrontiers in Microbiology
Volume8
Issue numberDEC
DOIs
StatePublished - Dec 5 2017

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Herpetic Stomatitis
Simian Immunodeficiency Virus
Human Herpesvirus 1
Macaca mulatta
Coinfection
Virus Diseases
Macaca
HIV
Human Herpesvirus 2
Viremia
T-Lymphocytes
Trigeminal Ganglion
Euthanasia
Cheek
Palatine Tonsil
DNA
Gingiva
Infection
Viral Load
Tongue

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

Cite this

Aravantinou, Meropi ; Mizenina, Olga ; Calenda, Giulia ; Kenney, Jessica ; Frank, Ines ; Lifson, Jeffrey D. ; Szpara, Moriah ; Jing, Lichen ; Koelle, David M. ; Teleshova, Natalia ; Grasperge, Brooke ; Blanchard, James ; Gettie, Agegnehu ; Martinelli, Elena ; Derby, Nina. / Experimental oral herpes simplex Virus-1 (HSV-1) co-infection in Simian Immunodeficiency Virus (SIV)-infected rhesus macaques. In: Frontiers in Microbiology. 2017 ; Vol. 8, No. DEC.
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abstract = "Herpes simplex virus 1 and 2 (HSV-1/2) similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV) transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP) models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.",
author = "Meropi Aravantinou and Olga Mizenina and Giulia Calenda and Jessica Kenney and Ines Frank and Lifson, {Jeffrey D.} and Moriah Szpara and Lichen Jing and Koelle, {David M.} and Natalia Teleshova and Brooke Grasperge and James Blanchard and Agegnehu Gettie and Elena Martinelli and Nina Derby",
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Aravantinou, M, Mizenina, O, Calenda, G, Kenney, J, Frank, I, Lifson, JD, Szpara, M, Jing, L, Koelle, DM, Teleshova, N, Grasperge, B, Blanchard, J, Gettie, A, Martinelli, E & Derby, N 2017, 'Experimental oral herpes simplex Virus-1 (HSV-1) co-infection in Simian Immunodeficiency Virus (SIV)-infected rhesus macaques', Frontiers in Microbiology, vol. 8, no. DEC, 2342. https://doi.org/10.3389/fmicb.2017.02342

Experimental oral herpes simplex Virus-1 (HSV-1) co-infection in Simian Immunodeficiency Virus (SIV)-infected rhesus macaques. / Aravantinou, Meropi; Mizenina, Olga; Calenda, Giulia; Kenney, Jessica; Frank, Ines; Lifson, Jeffrey D.; Szpara, Moriah; Jing, Lichen; Koelle, David M.; Teleshova, Natalia; Grasperge, Brooke; Blanchard, James; Gettie, Agegnehu; Martinelli, Elena; Derby, Nina.

In: Frontiers in Microbiology, Vol. 8, No. DEC, 2342, 05.12.2017.

Research output: Contribution to journalArticle

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T1 - Experimental oral herpes simplex Virus-1 (HSV-1) co-infection in Simian Immunodeficiency Virus (SIV)-infected rhesus macaques

AU - Aravantinou, Meropi

AU - Mizenina, Olga

AU - Calenda, Giulia

AU - Kenney, Jessica

AU - Frank, Ines

AU - Lifson, Jeffrey D.

AU - Szpara, Moriah

AU - Jing, Lichen

AU - Koelle, David M.

AU - Teleshova, Natalia

AU - Grasperge, Brooke

AU - Blanchard, James

AU - Gettie, Agegnehu

AU - Martinelli, Elena

AU - Derby, Nina

PY - 2017/12/5

Y1 - 2017/12/5

N2 - Herpes simplex virus 1 and 2 (HSV-1/2) similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV) transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP) models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

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