Regulated expression of galectin-1 after in vitro productive infection with herpes simplex virus type 1: implications for T cell apoptosis.

Apoptosis of cytotoxic T lymphocytes by herpes simplex virus type-1 (HSV-1) has been reported to be a relevant mechanism of viral immune evasion. Galectin-1 (Gal-1), an endogenous lectin involved in T-cell apoptosis, has recently gained considerable attention as a novel mechanism of tumor-immune evasion. Here we investigated whether infection of cells with HSV-1 can modulate the expression of Gal-1. Results show that pro-apoptotic Gal-1, but not Gal-3, is remarkably up-regulated in cell cultures infected with HSV-1. In addition, this protein is secreted to the extracellular milieu, where it contributes to apoptosis of activated T cells in a carbohydrate-dependent manner. Since many viruses have evolved mechanisms to counteract the antiviral response raised by the infected host, our results suggest that HSV-1 may use galectin-1 as a weapon to kill activated T cells and evade specific immune responses.

Pathogenesis of herpes simplex virus type 2 experimental genital infection in pregnant mice.

The progression of herpes simplex-2 genital infection in pregnant mice was studied by detection of viral antigens using immunoperoxidase in tissue sections, electron microscopy and virus isolation. The majority of mice (66.66%) died at 8-9 days post-inoculation. Abortions were observed in 69.23% of the infected mice along with impairment of labor and delivery. Herpes antigens were detected in most of the autonomic nerves of the uterus, including those surrounding small arterioles in the myometrium and the Auerbach and Meissner plexa of the large bowel, but not in the abortions or placentas. The infection of uterine autonomic fibers and myometrial cells could explain the delivery impairment and could have provoked a decrease in blood flow leading to abortions.

Progression of intravaginal infection by herpes simplex-2 in genetically athymic mice.

The purpose of this paper was to study the pathogenesis of wild-type Herpes simplex-2 (HSV-2) primary intravaginal (IVAG) infection in genetically athymic (nude) mice. Nude (nu/nu) N: NIH(S) and Balb/c mice, as well as their euthymic counterparts were IVAG infected with 5 x 10(5) pfu of HSV-2. The progression of the infection was followed by HSV-2 immunolabeling using the peroxidase-antiperoxidase technique in tissue sections of the whole body, electron microscopy, and viremia titration at two different time points. 70% of athymic NIH mice, 30% of euthymic NIH mice, and 80% of both athymic and euthymic Balb/c mice developed acute vulvovaginitis and died between 8-10 days post-infection (pi). Viremia was not detected in either athymic or euthymic mice. HSV-2 replicated in the vulvovaginal, vesical and perianal epithelia, then progressed towards the central nervous system mainly along autonomic nerves and ganglia. HSV-2 antigens were not detected in liver, spleen, kidney, skin, heart, lung or bone marrow. The conclusion is that the T-cell immune response seems to limit the IVAG infection of NIH mice at the inoculation site, but is not involved in preventing HSV-2 dissemination through the blood.

Immunocytochemical and morphological effects of short-term stimulation of cultured astrocytes.

Both image analysis at light microscopy level and ultrastructural characterization by transmission electron microscopy were employed to evaluate the differentiation stage in young cultured mouse astrocytes after 1-day exposure to dBcAMP, a chemical compound known to induce cell activation. The aim was to validate an experimental model of stimulated astrocytes preserving the properties of recently seeded cells, thus avoiding the overlapping effects of in vitro aging. Differentiated astrocytes, as evidenced by GFAP labeling by streptavidin-peroxidase, doubled their number in treated cultures (45%) versus controls (23%). In addition, a significant increase in process-bearing astrocytes (elongated and remified forms) to the detriment of immature polygonal astrocytes, was recorded. No noticeable changes were found in cell perimeter, but cell area displayed a significant reduction in labeled surface of astrocytes undergoing morphological differentiation. Concomitantly, electron microscopy showed that radially organized bundles of numerous intermediate filaments compatible with GFAP replaced the few scattered structures observed in control cultures. However, methodological caution is advisable as regards the relevance of this in vitro counterpart of in situ reactive astrocytes, since cell plasticity is recognized to depend on culture conditions. At any rate, present quantitative results demonstrate that GFAP-positive cell percentage and cell area measurement are adequate parameters of early immunocytochemical and morphological differentiation, respectively, and thus contribute to a better histometric characterization of an easily available substrate to discriminate the wide variety of factors involved in CNS response to injury.

Autonomic nervous system involvement in experimental genital infection by herpes simplex virus type 2.

Peroxidase-antiperoxidase technique and histology were employed to elucidate the peripheral routes involved in HSV-2 progression from vagina towards the central nervous system in mice. 12 week-old female Balb/c mice were intravaginally infected with 5 X 10(5)LD50 of HSV-2. Sixty per cent of animals developed vulvovaginitis, perigenital alopecia and hind-limb paresia. Death occurred at 9-11 days post-infection. Colon dilatation and urinary bladder distention were observed in all cases. Complete transversal sections from vulva to kidneys were obtained of each animal, including the spinal cord in situ. Herpes antigen were regularly detected in vulvovaginal epithelium, intramural, perigenital and perivesical small nerves. Besides, their invariable presence in Auerbach's plexus and sympathetic ganglia, strongly suggests preferential autonomic nervous system involvement in the progression of HSV-2 intravaginal infection towards the spinal cord.