A model of genital herpes simplex virus Type 1 infection in Rhesus Macaques
Meropi Aravantinou
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorInes Frank
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorGeraldine Arrode-Bruses
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorMoriah Szpara
The Pennsylvania State University, University Park, PA, USA
Search for more papers by this authorBrooke Grasperge
Tulane National Primate Research Center, Tulane University, Covington, LA, USA
Search for more papers by this authorJames Blanchard
Tulane National Primate Research Center, Tulane University, Covington, LA, USA
Search for more papers by this authorAgegnehu Gettie
Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY, USA
Search for more papers by this authorNina Derby
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorCorresponding Author
Elena Martinelli
Center for Biomedical Research, Population Council, New York, NY, USA
Correspondence
Elena Martinelli, Population Council, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorMeropi Aravantinou
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorInes Frank
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorGeraldine Arrode-Bruses
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorMoriah Szpara
The Pennsylvania State University, University Park, PA, USA
Search for more papers by this authorBrooke Grasperge
Tulane National Primate Research Center, Tulane University, Covington, LA, USA
Search for more papers by this authorJames Blanchard
Tulane National Primate Research Center, Tulane University, Covington, LA, USA
Search for more papers by this authorAgegnehu Gettie
Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY, USA
Search for more papers by this authorNina Derby
Center for Biomedical Research, Population Council, New York, NY, USA
Search for more papers by this authorCorresponding Author
Elena Martinelli
Center for Biomedical Research, Population Council, New York, NY, USA
Correspondence
Elena Martinelli, Population Council, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorFunding information
This work was supported by NIH grants R01 AI098456-04 and OD011104.
Abstract
Background
Although HSV-2 is the major cause of genital lesions, HSV-1 accounts for half of new cases in developed countries.
Methods
Three healthy SHIV-SF162P3-infected Indian rhesus macaques were inoculated with 4×108 pfu of HSV-1 twice, with the second inoculation performed after the vaginal mucosa was gently abraded with a cytobrush.
Results
HSV-1 DNA was detected in vaginal swabs 5 days after the second but not the first inoculation in all three macaques. An increase in inflammatory cytokines was detected in the vaginal fluids of the animals with no or intermittent shedding. Higher frequency of blood α4β7high CD4+ T cells was measured in the animals with consistent and intermitted shedding, while a decrease in the frequency of CD69+ CD4+ T cells was present in all animals.
Conclusions
This macaque model of genital HSV-1 could be useful to study the impact of the growing epidemic of genital HSV-1 on HIV infection.
REFERENCES
- 1Groves MJ. Genital herpes: a review. Am Fam Physician. 2016; 93: 928-934.
- 2Pellett PE, Roizman B. Herpesviridae. In: DM Knipe, PM Howley, eds. Fields Virology, 6th ed Philadelphia. PA: Lippincott Williams & Wilkins; 2013: pp. 1802-1822.
- 3Looker KJ, Magaret AS, May MT, et al. Global and regional estimates of prevalent and incident herpes simplex virus Type 1 infections in 2012. PLoS ONE. 2015; 10: e0140765. Epub 2015/10/29. https://doi.org/10.1371/journal.pone.0140765. PubMed PMID: 26510007; PubMed Central PMCID: PMCPMC4624804.
- 4Liu F, Zhou ZH. Comparative virion structures of human herpesviruses. In: A Arvin, G Campadelli-Fiume, E Mocarski, et al., eds. Human Herpesviruses: biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press; 2007.
10.1017/CBO9780511545313.004 Google Scholar
- 5Bradley H, Markowitz LE, Gibson T, McQuillan GM. Seroprevalence of herpes simplex virus types 1 and 2–United States, 1999-2010. J Infect Dis. 2014; 209: 325-333. Epub 2013/10/19. https://doi.org/10.1093/infdis/jit458. PubMed PMID: 24136792.
- 6Xu F, Lee FK, Morrow RA, et al. Seroprevalence of herpes simplex virus type 1 in children in the United States. J Pediatr. 2007; 151: 374-377. Epub 2007/09/25. https://doi.org/10.1016/j.jpeds.2007.04.065. PubMed PMID: 17889072.
- 7Jr Gnann JW, Whitley RJ. Clinical practice. Genital herpes. N Eng J Med. 2016; 375: 666-674. Epub 2016/08/18. https://doi.org/10.1056/nejmcp1603178. PubMed PMID: 27532832.
- 8Ryder N, Jin F, McNulty AM, Grulich AE, Donovan B. Increasing role of herpes simplex virus type 1 in first-episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992-2006. Sex Transm Infect. 2009; 85: 416-419. Epub 2009/03/11. https://doi.org/10.1136/sti.2008.033902. PubMed PMID: 19273479.
- 9Bernstein DI, Bellamy AR, Hook EW3rd, et al. Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women. Clin Infect Dis. 2013; 56: 344-351. Epub 2012/10/23. https://doi.org/10.1093/cid/cis891. PubMed PMID: 23087395; PubMed Central PMCID: PMCPMC3540038.
- 10Fenton KA, Imrie J.Increasing rates of sexually transmitted diseases in homosexual men in Western Europe and the United States: why?. Infect Dis Clin North Am. 2005; 19: 311-331. Epub 2005/06/21. https://doi.org/10.1016/j.idc.2005.04.004. PubMed PMID: 15963874.
- 11Harrison A, Colvin CJ, Kuo C, Swartz A, Lurie M. Sustained high HIV incidence in young women in Southern Africa: social, behavioral, and structural factors and emerging intervention approaches. Curr HIV/AIDS Rep. 2015; 12: 207-215. Epub 2015/04/10. https://doi.org/10.1007/s11904-015-0261-0. PubMed PMID: 25855338; PubMed Central PMCID: PMCPMC4430426.
- 12Corey L. Synergistic copathogens–HIV-1 and HSV-2. N Engl J Med. 2007; 356: 854-856. PubMed PMID: 17314346.
- 13Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. Aids. 2006; 20: 73-83. PubMed PMID: 16327322.
- 14Barnabas RV, Wasserheit JN, Huang Y, et al. . Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study). J Acquir Immune Defic syndr (1999). 2011; 57: 238-244. Epub 2011/08/24. https://doi.org/10.1097/qai.0b013e31821acb5. PubMed PMID: 21860356; PubMed Central PMCID: PMCPMC3446850.
- 15Zhu J, Hladik F, Woodward A, et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nat Med. 2009; 15: 886-892. PubMed PMID: 19648930.
- 16Celum C, Wald A, Lingappa JR, et al. Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl J Med. 2010; 362: 427-439. https://doi.org/10.1056/NEJMoa0904849. PubMed PMID: 20089951; PubMed Central PMCID: PMC2838503.
- 17Crostarosa F, Aravantinou M, Akpogheneta OJ, et al. A macaque model to study vaginal HSV-2/immunodeficiency virus co-infection and the impact of HSV-2 on microbicide efficacy. PLoS ONE. 2009; 4: e8060. Epub 2009/12/17. https://doi.org/10.1371/journal.pone.0008060. PubMed PMID: 20011586; PubMed Central PMCID: PMC2787245.
- 18Martinelli E, Veglia F, Goode D, et al. The frequency of alpha4beta7high memory CD4+ T cells correlates with susceptibility to rectal SIV infection. J Acquir Immune Defic Syndr (1999). 2013; 64: 325-331. https://doi.org/10.1097/qai.0b013e31829f6e1a. PubMed PMID: 23797688.
- 19Goode D, Truong R, Villegas G, et al. HSV-2-driven increase in the expression of alpha4beta7 correlates with increased susceptibility to vaginal SHIV(SF162P3) infection. PLoS Pathog. 2014; 10: e1004567. Epub 2014/12/19. https://doi.org/10.1371/journal.ppat.1004567. PubMed PMID: 25521298; PubMed Central PMCID: PMCPMC4270786.
- 20Guerra-Perez N, Aravantinou M, Veglia F, et al. Rectal HSV-2 infection may increase rectal SIV acquisition even in the context of SIVDeltanef vaccination. PLoS ONE. 2016; 11: e0149491. Epub 2016/02/18. https://doi.org/10.1371/journal.pone.0149491. PubMed PMID: 26886938; PubMed Central PMCID: PMCPMC4757571.
- 21Smith G. Herpesvirus transport to the nervous system and back again. Annu Rev Microbiol. 2012; 66: 153-176. Epub 2012/06/26. https://doi.org/10.1146/annurev-micro-092611-150051. PubMed PMID: 22726218; PubMed Central PMCID: PMCPMC3882149.
- 22Kollias CM, Huneke RB, Wigdahl B, Jennings SR. Animal models of herpes simplex virus immunity and pathogenesis. J Neurovirol. 2015; 21: 8-23. Epub 2014/11/13. https://doi.org/10.1007/s13365-014-0302-2. PubMed PMID: 25388226.
- 23Varnell ED, Kaufman HE, Hill JM, Wolf RH. A primate model for acute and recurrent herpetic keratitis. Curr Eye Res. 1987; 6: 277-279. Epub 1987/01/01 PubMed PMID: 3829703.
- 24Rootman DS, Haruta Y, Hill JM. Reactivation of HSV-1 in primates by transcorneal iontophoresis of adrenergic agents. Invest Ophthalmol Vis Sci. 1990; 31: 597-600. Epub 1990/03/01 PubMed PMID: 2156785.
- 25Deisboeck TS, Wakimoto H, Nestler U, et al. Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study. Gene Ther. 2003; 10: 1225-1233. Epub 2003/07/15. https://doi.org/10.1038/sj.gt.3302003. PubMed PMID: 12858187.
- 26Sekulin K, Jankova J, Kolodziejek J, et al. Natural zoonotic infections of two marmosets and one domestic rabbit with herpes simplex virus type 1 did not reveal a correlation with a certain gG-, gI- or gE genotype. Clin Microbiol Infect. 2010; 16: 1669-1672. Epub 2010/02/04. https://doi.org/10.1111/j.1469-0691.2010.03163.x. PubMed PMID: 20121821.
- 27Schrenzel MD, Osborn KG, Shima A, Klieforth RB, Maalouf GA. Naturally occurring fatal herpes simplex virus 1 infection in a family of white-faced saki monkeys (Pithecia pithecia pithecia). J Med Primatol. 2003; 32: 7-14. Epub 2003/05/08 PubMed PMID: 12733597.
- 28Huemer HP, Larcher C, Czedik-Eysenberg T, Nowotny N, Reifinger M. Fatal infection of a pet monkey with human herpesvirus. Emerg Infect Dis. 2002; 8: 639-642. Epub 2002/05/25. https://doi.org/10.3201/eid0806.010341. PubMed PMID: 12023925; PubMed Central PMCID: PMCPMC2738492.
- 29Macdonald SJ, Mostafa HH, Morrison LA, Davido DJ. Genome sequence of herpes simplex virus 1 strain McKrae. J Virol. 2012; 86: 9540-9541. Epub 2012/08/11. https://doi.org/10.1128/jvi.01469-12. PubMed PMID: 22879612; PubMed Central PMCID: PMCPMC3416131.
- 30Dix RD, McKendall RR, Baringer JR. Comparative neurovirulence of herpes simplex virus type 1 strains after peripheral or intracerebral inoculation of BALB/c mice. Infect Immun. 1983; 40: 103-112. Epub 1983/04/01. PubMed PMID: 6299955; PubMed Central PMCID: PMCPMC264823.
- 31Wang H, Davido DJ, Morrison LA. HSV-1 strain McKrae is more neuroinvasive than HSV-1 KOS after corneal or vaginal inoculation in mice. Virus Res. 2013; 173: 436-440. Epub 2013/01/24. https://doi.org/10.1016/j.virusres.2013.01.001. PubMed PMID: 23339898; PubMed Central PMCID: PMCPMC3640688.
- 32Cline AN, Bess JW, Jr Piatak M, Lifson JD. Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS. J Med Primatol. 2005; 34: 303-312. PubMed PMID: 16128925.
- 33Martinelli E, Tharinger H, Frank I, et al. HSV-2 infection of dendritic cells amplifies a highly susceptible HIV-1 cell target. PLoS Pathog. 2011; 7: e1002109. Epub 2011/07/09. https://doi.org/10.1371/journal.ppat.1002109. PubMed PMID: 21738472; PubMed Central PMCID: PMC3128120.
- 34Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N. Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol. 2003; 73: 713-721. Epub 2003/05/30 PubMed PMID: 12773503.
- 35Shin H, Iwasaki A. Generating protective immunity against genital herpes. Trends Immunol. 2013; 34: 487-494. Epub 2013/09/10. https://doi.org/10.1016/j.it.2013.08.001. PubMed PMID: 24012144; PubMed Central PMCID: PMCPMC3819030.
- 36Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature. 2009; 462: 510-513. Epub 2009/11/10. https://doi.org/10.1038/nature08511. PubMed PMID: 19898495; PubMed Central PMCID: PMCPMC2789415.
- 37Sandgren KJ, Bertram K, Cunningham AL. Understanding natural herpes simplex virus immunity to inform next-generation vaccine design. Clin Transl Immunology. 2016; 5: e94. Epub 2016/08/16. https://doi.org/10.1038/cti.2016.44. PubMed PMID: 27525067; PubMed Central PMCID: PMCPMC4973325.
- 38Pitcher CJ, Hagen SI, Walker JM, et al. Development and homeostasis of T cell memory in rhesus macaque. J Immunol. 2002; 168: 29-43.