Immunological hiding of herpesvirus-infected cells

Summary.  Over the past years, numerous research groups have discovered various strategies that herpesviruses use to hide themselves from recognition by the immune system of their hosts. The current review gives a summary of this research, with emphasis on the mechanisms by which herpesvirus-infected cells escape from elimination by complement, phagocytes, cytotoxic T-lymphocytes and/or natural killer cells. Accepted March 2, 2000     

Lysis of herpesvirus-infected cells by immune spleen cells.

Spleen cells from herpes simplex-infected mice have been shown to lyse 51Cr-labeled virus-infected target cells. The cell-mediated lysis was shown to be antibody dependent but not involving adherent cells. Lysis of infected cells by this mechanism may be one form of host defense in infection by some viruses.     

Phospholipid metabolism induced by Clostridium perfringens alpha-toxin elicits a hot-cold type of hemolysis in rabbit erythrocytes.

GTP and AIF4- significantly stimulated the late phosphatidic acid (PA) formation induced by Clostridium perfringens alpha-toxin in rabbit erythrocyte lysates. Pertussis toxin blocked the PA production. AIF4- markedly enhanced phosphatidylethanol production induced by alpha-toxin in the presence of ethanol. GTP[gamma S] stimulated the PA formation and hemolysis induced by alpha-toxin, and GDP[beta S] inhibited them. An H-to-G mutation at position 126 (H126G) induced the PA formation and hemolysis in a Co2+ concentration-dependent manner. H148G induced neither the PA formation nor hemolysis. These results suggest that the toxin-induced hemolysis is due to activation of phospholipid metabolism systems through GTP-binding protein.     

Enhancement of antibody-dependent cell-mediated cytotoxicity of herpesvirus-infected cells by complement.

An investigation was made of the effects of complement on the levels of antibody-dependence cytotoxicity (ADCC) mediated by bovine leukocytes against herpesvirus-infected target cells. Neutrophil-mediated ADCC was considerably enhanced upon the addition of low levels of complement that alone failed to induce lysis of antibody-sensitized target cells. This enhancement was most apparent under suboptimum conditions such as at low effector-to-target cell ratios, low levels of sensitizing antiserum, and short-duration assays. Furthermore, cells and classes of immunoglobulin unable to induce ADCC could do so in the presence of complement. The action of complement is considered in terms of a more tenacious bond formed between effector and target cells. The implications of the results are discussed in terms of the part that complement might play in enhancing antiviral recovery processes.     

Phospholipid metabolism of cultured Trichomonas vaginalis and Tritrichomonas foetus

Trichomonas vaginalis and Tritrichomonas foetus grown in a fetal calf serum-based culture medium were exposed to radiolabeled phospholipids and lipid precursors to determine the extent to which these organisms can incorporate complex lipids and/or de novo synthesize their major membrane phosphoglycerides. Phosphatidylethanolamine and phosphatidylcholine were the dominant phospholipids (40-50% of extractable phospholipids), with acidic lipids, phosphatidylinositol, phosphatidylserine, phosphatidylglycerol and O-acylphosphatidylglycerol accounting for the remaining phosphoglycerides. T. vaginalis was rich in sphingomyelin while T. foetus lacks significant amounts of this lipid. Incubation with [32P]orthophosphate resulted in only modest incorporation into extractable phospholipids; the most striking observation being the failure to label choline-containing lipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin). Phosphatidylethanolamine was heavily labeled with modest labeling observed in the acidic phosphoglycerides. [U-14C]Glucose failed to label choline-containing lipids in T. foetus but did so in T. vaginalis, with phosphatidylethanolamine again being heavily labeled. Choline, phosphorylcholine, ethanolamine, serine, inositol, glycerol and methionine were incorporated poorly or failed to label the expected phosphoglycerides in either of the trichomonads, demonstrating an impairment in synthesis. Intact phosphoglycerides, labeled in the fatty acyl groups, labeled most phospholipids indicating that turnover of membrane lipids can occur with respect to the acyl component of the phospholipids. Fluorescent probes attached to phosphoglyceride molecules support observations seen with radiolabeled phosphoglycerides. Though trichomonads are able to transacylate phosphoglycerides, it is evident that the trichomonads lack a variety of enzymatic activities necessary for de novo synthesis of complex phosphoglycerides and must rely on environmental sources to supply them.     

ATPase activity in macula densa cells of the rabbit kidney

Na-K- and Mg-activated ATPase activities were determined in maculae densae and glomeruli dissected from both superficial and juxtamedullary nephrons of normal rabbits, using an ultramicro method including a cycling reaction. Activities were expressed as P_i generated per macula densa or per glomerulus and normalized for tissue volume. Results indicate that the mean volume of superficial and juxtamedullary macula densa samples was not statistically different, while glomeruli from deep nephrons had sample volumes that were 29% larger than those from superficial nephrons (P<0.001). Correcting for volume both superficial and juxtamedullary macula densa samples had an Na-K-ATPase activity of 0.37±0.21 fmol · h^–1 · (m³)^–1. Mg-ATPase activity in both pools was also similar [0.41±0.07 and 0.52±0.1 fmol · h^–1 · (m³)^–1]. Na-K-ATPase activity in macula densa cells is estimated to be about 1/40th the activity of surrounding cortical thick ascending limb cells. Total glomerular ATPase per unit volume was significantly higher in glomeruli from superficial than from deep nephrons [0.41±0.04 vs. 0.28±0.04 fmol · h^–1 · (m³)^–1 P<0.05]. There was no statistically significant activity of Na-K-ATPase in either superficial or deep glomeruli. These results suggest that in contrast to previous reports, the macula densa contains Na-K-ATPase, but at a low level relative to surrounding tubular cells. Further, in normal rabbits, this activity is invariant in superficial and juxtamedullary samples.     

Possible pitfalls in the study of IgG receptors produced by herpesvirus-infected cells

Summary The presence of specific antibodies to human herpesviruses in certain purified human IgG preparations from commercial sources may produce misleading results when such preparations are used in studies on the IgG receptors produced by virus-infected cells.This study was supported by Public Health Service Grant AI-01475 from the National Institute of Allergy and Infectious Diseases.     

DNA-dependent DNA polymerase pattern in noninfected and herpesvirus infected rabbit kidney cells

Summary In this paper we report on a DNA-dependent DNA polymerase produced in herpesvirus infected cells which is not present in virions. It differs from the polymerases of noninfected cells by its molecular weight as well as by its insensitivity to cytosine arabinoside triphosphate (ara-CTP).     

Alterations of uninfected red blood cells in malaria

Red blood cell (RBC) negative charges and resistance to linoleic acid (LNA)-induced lysis were studied inPlasmodium yoelii-infected mice and in malaria (P. falciparum)-affected individuals. RBCs from mice infected withP. yoelii showed a progressive decrease in the net surface negative charges at 24 h after infection, reaching a minimal value on day 3, followed by a second phase that was characterised by a recovery to normal levels on day 6. Resistance to linoleic acid follows similar kinetics. These alterations preceded the appearance of parasites in the peripheral blood. A similar increase in LNA-induced lysis was observed in RBCs from malaria-affected individuals. These early membrane alterations of uninfected RBCs could be responsible for spreading of infection and RBC lysis during infection.     

Comparison of human fibroblast cells and primary rabbit kidney cells for isolation of herpes simplex virus.

Human foreskin fibroblast cells and primary rabbit kidney cells were compared for efficiency in isolation of herpes simplex virus from 1,100 clinical specimens. Of the fibroblast cultures, 265 were positive, whereas 268 primary rabbit kidney cultures were positive. The results indicate that either cell type is acceptable for diagnostic use.     

磷脂多不饱和脂肪酸抑制兔耳增生性瘢痕

背景：多不饱和脂肪酸有抑制细胞炎症反应及免疫功能的作用,增生性瘢痕的形成与炎症、细胞免疫、细胞因子有着密切关系,但目前尚无应用多不饱和脂肪酸防治增生性瘢痕的实验研究。 目的：探讨磷脂多不饱和脂肪酸对兔耳增生性瘢痕的抑制作用。 方法：在9只新西兰大白兔兔耳腹侧做直径1 cm的圆形全层皮肤缺损创面,每侧6个,共108个,其中形成增生性瘢痕92个,瘢痕形成率为85%。实验分3组：每只兔耳靠前3个创面涂磷脂多不饱和脂肪酸霜,右耳靠后3个创面涂多磺酸黏多糖乳膏,创面上皮化后立即涂药,每日1次,左耳靠后3个创面自然愈合。分别在术后28,42,63,90 d,观察创面的愈合情况;显微镜下观察瘢痕组织的厚度、胶原纤维和成纤维细胞密度;免疫组织化学染色检测胶原纤维的表达。 结果与结论：涂抹磷脂多不饱和脂肪酸霜和多磺酸黏多糖乳膏可使增生性瘢痕体积缩小、厚度变薄、成纤维细胞密度减小、胶原纤维表达减少。尤以磷脂多不饱和脂肪酸霜的效果最为明显。说明磷脂多不饱和脂肪酸可抑制兔耳增生性瘢痕的形成,减轻瘢痕的增生程度。