抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer. It is proposed that these rafts function as platforms for the attachment of proteins when membranes are moved around inside the cell and during signal transduction.

Functional rafts in cell membranes

Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation, and aspects of cell growth control. Programmed cell death (apoptosis) is crucial for maintaining appropriate cell number and tissue organization. It was therefore of interest to determine whether cell-matrix interactions affect apoptosis. The present report demonstrates that apoptosis was induced by disruption of the interactions between normal epithelial cells and extracellular matrix. We have termed this phenomenon "anoikis." Overexpression of bcl-2 protected cells against anoikis. Cellular sensitivity to anoikis was apparently regulated: (a) anoikis did not occur in normal fibroblasts; (b) it was abrogated in epithelial cells by transformation with v-Ha-ras, v-src, or treatment with phorbol ester; (c) sensitivity to anoikis was conferred upon HT1080 cells or v-Ha-ras-transformed MDCK cells by reverse-transformation with adenovirus E1a; (d) anoikis in MDCK cells was alleviated by the motility factor, scatter factor. The results suggest that the circumvention of anoikis accompanies the acquisition of anchorage independence or cell motility.

/pdf/disruption-of-epithelial-cell-matrix-interactions-induces-4zrqjfm9bc.pdf

Disruption of epithelial cell-matrix interactions induces apoptosis

https://www.cell.com/cell/pdf/0092-8674(92)90189-J.pdf

Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface

Approximately one percent of the human genome encodes proteins that either regulate or are regulated by direct interaction with members of the Rho family of small GTPases. Through a series of complex biochemical networks, these highly conserved molecular switches control some of the most fundamental processes of cell biology common to all eukaryotes, including morphogenesis, polarity, movement, and cell division. In the first part of this review, we present the best characterized of these biochemical pathways; in the second part, we attempt to integrate these molecular details into a biological context.

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Rho GTPases: Biochemistry and Biology

The entry of fowl plague virus, and avian influenza A virus, into Madin-Darby canine kidney (MDCK) cells was examined both biochemically and morphologically. At low multiplicity and 0 degrees C, viruses bound to the cell surface but were not internalized. Binding was not greatly dependent on the pH of the medium and reached an equilibrium level in 60-90 min. Over 90% of the bound viruses were removed by neuraminidase but not by proteases. When cells with prebound virus were warmed to 37 degrees C, part of the virus became resistant to removal b neuraminidase, with a half-time of 10-15 min. After a brief lag period, degraded viral material was released into the medium. The neuraminidase-resistant virus was capable of infecting the cells and probably did so by an intracellular route, since ammonium chloride, a lysosomotropic agent, blocked both the infection and the degradation of viral protein. When the entry process was observed by electron microscopy, viruses were seen bound primarily to microvilli on the cell surface at 0 degrees C and, after warming at 37 degrees C, were endocytosed in coated pits, coated vesicles, and large smooth-surfaced vacuoles. Viruses were also present in smooth-surfaced invaginations and small smooth-surfaced vesicles at both temperatures. At physiological pH, no fusion of the virus with the plasma membrane was observed. When prebound virus was incubated at a pH of 5.5 or below for 1 min at 37 degrees C, fusion was, however, detected by ferritin immunolabeling. t low multiplicity, 90% of the prebound virus became neuraminidase-resistant and was presumably fused after only 30 s at low pH. These experiments suggest that fowl plague virus enters MDCK cells by endocytosis in coated pits and coated vesicles and is transported to the lysosome where the low pH initiates a fusion reaction ultimately resulting in the transfer of the genome into the cytoplasm. The entry pathway of fowl plague virus thus resembles tht earlier described for Semliki Forest virus.

https://rupress.org/jcb/article-pdf/91/3/601/1075680/601.pdf

Infectious entry pathway of influenza virus in a canine kidney cell line

Representatives of three families of enveloped viruses were shown to fuse tissue culture cells together. These were: Semliki Forest virus (SFV, a togavirus), vesicular stomatitis virus (a rhabdovirus), and two myxoviruses, fowl plaque virus and Japan influenza virus (Japan)/A/305/57). Unlike paramyxoviruses, whose fusion activity is known to occur over a broad pH range, fusion by these viruses was restricted to mildly acidic pH. The pH thresholds for the four viruses were 6.0, 6.1, 5.5, and 5.1, respectively. The precursor form of Japan influenza, which is not infectious and which contains the uncleaved hemagglutinin, had no fusion activity. This result suggested a role for the influenza hemagglutinin in the low-pH-dependent membrane fusion activity. Taken together, our results show that low-pH-induced fusion is a widespread property of enveloped animal viruses and that it may play a role in the infective process. The fusion reactions with all four viruses were fast, efficient, and easy to induce. With UV-inactivated SFV, the fusion was shown to be nonlytic and the polykaryons were viable for at least 12 h. 30 ng of SFV/1 x 10(6) BHK-21 cells were required for 50% fusion, and 250 ng sufficed to fuse the entire culture into a single polykaryon.

https://rupress.org/jcb/article-pdf/89/3/674/1074809/674.pdf

Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses.

Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation

The intracellular location at which the G protein of vesicular stomatitis virus accumulated when transport was blocked at 20 degrees C has been studied by biochemical, cytochemical, and immunocytochemical methods. Our results indicated that the viral G protein was blocked in that cisterna of the Golgi stack which stained for acid phosphatase. At 20 degrees C this trans cisterna became structurally altered by the accumulation of G protein. This alteration was characterized by extensive areas of membrane buds which were covered by a cytoplasmic coat. These coated structures were of two kinds--those that labeled with anti-clathrin antibodies and those that did not. The clathrin-coated pits consistently did not label with anti-G antibodies. Upon warming infected cells to 32 degrees C, G protein appeared on the surface within minutes. Concomitantly, the trans cisterna lost its characteristic structural organization. Double-labeling experiments were performed in which G protein localization was combined with staining for horseradish peroxidase, which had been taken up from the extracellular medium by endocytosis. The results suggest that the trans cisterna was distinct from the endosome compartment and that the latter was not an obligatory station in the route taken by G protein to the cell surface.

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Karl S. Matlin

Papers

Infectious entry pathway of influenza virus in a canine kidney cell line

Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses.

Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation

Exit of newly synthesized membrane proteins from the trans cisterna of the Golgi complex to the plasma membrane.

Pathway of vesicular stomatitis virus entry leading to infection