Asymptomatic vaginal herpes simplex virus infections in mice: virology and pathohistology

Abstract

One of the causes of genital tract infections in humans are herpes simplex virus types 1 and 2 (HSV-1, HSV-2). Although primary and recurrent infections can be clinically apparent and in part very serious, many infections are asymptomatic and result only in temporary genital shedding of virus (recurrences). During our investigations of vaginitis, strain IES of HSV-1 produced an asymptomatic infection. Replication in the murine vaginal (vag.) epithelium as well as antibody formation after vag. infection was comparable to those of survivors after infection with highly virulent strains. Titration of liver, spleen, ovaries, adrenal glands spinal cord, or brain after vag. IES infection revealed no virus, whereas after i.p. infection virus could be demonstrated in many organs examined. Histological examination with a DNA probe (in situ hybridisation), HSV antibodies (immunohistochemistry), and haematoxylin and eosin (HE) staining showed only small focal HSV lesions of the vaginal epithelium in early stages of the infection, never exceeding to the subepithelial tissue. Severe infiltrations and ulcerations after infection with highly virulent strains (17syn +, ER-) could never be demonstrated after IES vag. infection. Identical replication rates of both groups of HSV despite much greater areas of epithelial necrosis with the virulent strains may be explained by the large number of virus inactivating granulocytes induced by the virulent strains, thus inactivating the hypothetical higher virus load.

Endocrine Aspects of Cancer Gene Therapy

“…In the ovaries, lesions were detected in follicles and in the stroma. During the course of infection, HSV nucleic acids and proteins could be detected in adrenal and ovary lesions, but there was no evidence of HSV latency in either organ (514,530,532).…”

“…After vaginal infections of mice with neuroinvasive strains of HSV-1 and HSV-2, virus replicates in the vaginal epithelium, in the paravaginal ganglia, in the spinal cord, and finally in the brain and the adrenal glands (516,532). However, viral antigens could be demonstrated only in the medulla of the adrenal glands but not in the cortex (532).…”

“…The adrenal gland is a major target of HSV-1 infection. The propensity of HSV to localize in the adrenals was demonstrated after several routes of administration in animal models, including intranasal (525), sc (526), iv (517,527,528), ip (529 -531), vaginal (516,532), and intraocular injection (515). Experimental intranasal infection of mice with wild-type HSV-1, VR3 strain, was constantly followed by interstitial pneumonia and adrenal necrosis, often leading to death (525).…”

HSV-1 strain McKrae is more neuroinvasive than HSV-1 KOS after corneal or vaginal inoculation in mice

“…In one study comparing i.vag. inoculation of HSV-1 strain 17syn+ to strain IES, a thymidine kinase-deficient mutant (Muller et al, 1979), 17syn+ replicated for a prolonged period in the genital mucosa, caused severe vaginitis, and spread more readily to the nervous system (Podlech et al, 1996). Taken together, these observations suggest strain- and route-dependent differences in HSV-1 neuroinvasiveness.…”

Induction of Cyclooxygenase (COX)‐2 in Human Vaginal Epithelial Cells in Response to TLR ligands and TNF‐α

“…6,7 TLR2 may form heterodimers with other TLRs. 33,34 This could be attributed to a weak mucosal inflammatory reaction triggered by these infections, resulting in low mucosal COX-2 stimulation and PGE 2 production. [25][26][27][28] TLR3 is involved in the recognition of viral antigens such as dsRNA, which is formed during viral replication.…”