The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

Abstract

As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1. Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection, and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG) on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

Outbreak of Encephalitis Caused by Human Herpesvirus Type 1 (HSV-1) in NonHuman Captive Primates in São Paulo, SP, Brazil

“…We also noted the presence of marked desquamative monolymphocytic enterocolitis in the small intestine of the primates of our study, which was also reported in the intestine of Alouatta caraya by Barnes et al, in the intestine and stomach of C. jacchus and C. penicillata by Casagrande et al and A. azarae by Kreutzer et al [11,20,35]. Fan et al, however, stated that in the structural damage was observed in the brain and other organs of the M. mullata inoculated with HSV-1 [15]. These authors suggested that HSV-1 infection was capable of inducing vesicular lesions in the oral skin or mucosa of mediating viral replication at least in nervous tissues through an unknown mechanism without pathological damage.…”

“…The herpesvirus was isolated in Vero cells in brain samples from the marmosets and the cytopathic effects observed were, cells decrease with rounding, refringence and detachment in 2 days, aspects also observed in other studies of HSV-1 in C. jacchus, Hylobates a. agilus and in M. mulatta [13,15,38]. To the transmission electron microscope, we visualized by means of negative staining, typical particles of herpesvirus, isometric, exhibits enveloped and non-enveloped particles, showing nucleocapsids stain penetrated and non-strain penetrated, measuring 120-200 nm of diameter.…”

“…HSV-1 shows 79% nucleotide sequence identity with monkey B virus, a zoonosis that results in encephalitis or neurological problems in humans, with the majority of monkeys being asymptomatic carriers [10]. Outbreaks of the disease have been reported in various parts of the world, as USA; Germany; Austria; Peru; Thailand; China; Japan and Espanha [4,5,[11][12][13][14][15][16][17]. In Brazil, few reports describe the occurrence of HSV-1 in non-human primates, but all affecting marmosets (Callithrix jacchus and Callithrix penicillata) [6,[18][19][20][21].…”

Experimental Oral Herpes Simplex Virus-1 (HSV-1) Co-infection in Simian Immunodeficiency Virus (SIV)-Infected Rhesus Macaques

“…This is due at least in part to the absence of a relevant animal model for studying oral HSV-1 co-infection in the context of HIV infection. Only one recent study described oral HSV-1 infection in rhesus macaques (Fan et al, 2017 ), and this was in the absence of SIV. The majority of NHP studies of HSV-1 infection have used new world NHPs, with highly pathogenic outcomes (Kaufman, 1963 ; Katzin et al, 1967 ; Varnell et al, 1987 , 1995 ; Rootman et al, 1990 ; Hunter et al, 1999 ; Deisboeck et al, 2003 ).…”

“…Thus, these models are inadequate for studying HSV-1 immunology as it relates to humans or HSV-1/SIV co-infection. Only one recent report described oral HSV-1 infection in rhesus macaques after lip scarification (Fan et al, 2017 ), and we recently described genital HSV-1 infection in SHIV-infected macaques (Aravantinou et al, 2017 ).…”