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

J. Appl. Cryst.の発刊に際して

Lincoln, Yvonna, and Egon Guba, "Postpositivism and the Naturalist Paradigm," pp. 14-46 in Yvonna Lincoln and Egon Guba, Naturalistic Inquiry . Beverly Hills, CA: Sage, 1985.*

Evolution of Protein Molecules

Epstein-Barr virus.

Many pandemics have been attributed to the ability of some RNA viruses to change their host range to include humans. Here, we review the mechanisms of disease emergence that are related to the host-range specificity of selected mosquito-borne alphaviruses and flaviviruses. We discuss viruses of medical importance, including Venezuelan equine and Japanese encephalitis viruses, dengue viruses and West Nile viruses.

/pdf/transmission-cycles-host-range-evolution-and-emergence-of-2j0r7khe5z.pdf

Transmission cycles, host range, evolution and emergence of arboviral disease.

Since it emerged in Japan in the 1870s, Japanese encephalitis has spread across Asia and has become the most important cause of epidemic encephalitis worldwide. Four genotypes of Japanese encephalitis virus (JEV) are presently recognized (representatives of genotypes I to III have been fully sequenced), but its origin is not known. We have determined the complete nucleotide and amino acid sequence of a genotype IV Indonesian isolate (JKT6468) which represents the oldest lineage, compared it with other fully sequenced genomes, and examined the geographical distribution of all known isolates. JKT6468 was the least similar, with nucleotide divergence ranging from 17.4 to 19.6% and amino acid divergence ranging from 4.7 to 6.5%. It included an unusual series of amino acids at the carboxy terminus of the core protein unlike that seen in other JEV strains. Three signature amino acids in the envelope protein (including E327 Leu-->Thr/Ser on the exposed lateral surface of the putative receptor binding domain) distinguished genotype IV strains from more recent genotypes. Analysis of all 290 JEV isolates for which sequence data are available showed that the Indonesia-Malaysia region has all genotypes of JEV circulating, whereas only more recent genotypes circulate in other areas (P < 0.0001). These results suggest that JEV originated from its ancestral virus in the Indonesia-Malaysia region and evolved there into the different genotypes which then spread across Asia. Our data, together with recent evidence on the origins of other emerging viruses, including dengue virus and Nipah virus, imply that tropical southeast Asia may be an important zone for emerging pathogens.

Origin and Evolution of Japanese Encephalitis Virus in Southeast Asia

Through the Advisory Committee on Dengue and other Flavivirus Vaccines, the World Health Organization (WHO) has had a long-standing commitment to facilitate and to guide research and development of...

https://media.news.health.ufl.edu/misc/egh/cap & sari team/arbovirus sops/references/prnt.pdf

Guidelines for Plaque-Reduction Neutralization Testing of Human Antibodies to Dengue Viruses

Dengue viruses (DEN) (Flaviviridae: Flavivirus) are serious human pathogens that occur nearly throughout the tropics, with ca. 100 million cases annually (16). DEN comprise four serotypes (DEN-1 to DEN-4); although epidemiologically similar, they are genetically and antigenically distinct. Infection with one serotype leads to lifelong protection against homologous reinfection but only brief protection against heterologous challenge (21, 38).

DEN cause dengue fever, a self-limited febrile illness lasting 2 to 10 days that has been known in the medical literature for over 200 years. Infrequent epidemics of dengue fever occurred in tropical areas until the 1950s. After War World II, this pattern of disease was disrupted by the emergence of dengue hemorrhagic fever and dengue shock syndrome, more severe diseases characterized by thrombocytopenia, hemorrhage, and excessive plasma leakage (16, 28). Two principal hypotheses have been proposed to explain the hemorrhagic form of disease: (i) the immune enhancement theory maintains that hemorrhage occurs in secondary infections when DEN-specific antibodies and memory T cells resulting from primary infection with another serotype enhance the binding of virus-immunoglobulin G complexes to FcY receptors on monocytic cells, and (ii) certain phenotypes of DEN are more virulent than others. Recent phylogenetic studies suggest that an Asian genotype of DEN-2 recently introduced into the New World may be associated with increased risk for hemorrhagic fever and shock in the presence of heterologous antibody (32). DEN strains of reduced virulence have also been described; endemic transmission on the South Pacific islands of Tonga, involving vectors other than Aedes aegypti, may result in less severe disease because of the lesser selection for high viremia imposed by more susceptible vectors, like Aedes polynesiensis (13).

Two distinct DEN transmission cycles occur: (i) endemic and epidemic DEN involving human hosts and transmission by A. aegypti, with Aedes albopictus and other Aedes mosquitoes serving as secondary vectors, and (ii) a zoonotic or sylvatic cycle in sylvatic habitats of Africa and Malaysia, involving nonhuman primate reservoir hosts and several different Aedes mosquitoes (12, 16). Although A. aegypti plays a greater role in urban transmission, A. albopictus and some other secondary Aedes vectors are generally more susceptible to experimental infection (12). Considerable variation in susceptibility and transmission efficiency among geographic populations of both A. aegypti and A. albopictus has also been demonstrated (14, 15). A. aegypti has reinfested most of the neotropics since its partial eradication earlier this century, resulting in reemergence of neotropical dengue (13).

The sylvatic transmission cycles of DEN have received little study. In West Africa, nonhuman primate cycles have been identified in several countries. DEN-2 has been isolated from Aedes (S.) africanus, Aedes (S.) leuteocephalus, Aedes (S.) opok, Aedes (D.) taylori, and Aedes (D.) furcifer (5, 33). African DEN-2 sylvatic isolates are genetically distinct from all endemic/epidemic isolates and are believed to be evolutionarily distinct (12, 16, 31). In Malaysia, all four serotypes of DEN are maintained in canopy-dwelling Aedes niveus mosquitoes and nonhuman primates (34–37). DEN-1, -2, and -4 were isolated from sentinel monkeys, and monkey seroconversion was demonstrated against DEN-1, -2, and -3. DEN-4 was also isolated from canopy collections of A. niveus mosquitoes (35).

Gubler (13) has hypothesized that endemic/epidemic DEN evolved from sylvatic forms of the viruses that utilize nonhuman primate hosts and gallery forest Aedes vectors (i.e., not A. aegypti or A. albopictus). To test this hypothesis, we have sequenced the complete envelope (E) protein gene of DEN-1, -2, and -4 strains isolated in primary tropical forest habitats in Malaysia by Albert Rudnick and colleagues during the 1960s and 1970s (36, 37), as well as DEN-2 strains from sylvatic locations in West Africa analyzed previously using other, smaller genome regions (31). Phylogenetic analyses indicated that the endemic/epidemic lineages of DEN-1, -2, and -4 evolved independently from sylvatic viruses circulating in the Asian-Oceania region. Estimates of divergence times suggested that emergences of endemic/epidemic DEN occurred on the order of 100 to 1,500 years ago.

Evolutionary Relationships of Endemic/Epidemic and Sylvatic Dengue Viruses

Yellow fever virus (YFV) is the prototype member of the genus Flavivirus, a group of viruses that are transmitted between vertebrates by arthropod vectors. The virus is found in tropical regions of Africa and South America and is transmitted to primates by mosquitoes: Aedes spp. in Africa and Haemagogus and Sabethes spp. in South America. Despite the availability of an effective vaccine, yellow fever (YF) is considered a reemerging disease owing to its increased incidence in the past 25 years. Molecular epidemiologic data suggest there are seven genotypes of YFV that are geographically separated, and outbreaks of disease are more associated with particular genotypes. In addition, the risk of urban YF, owing to transmission of the virus by Aedes aegypti, is increasing in Africa, as is the potential of urban YF returning to South America. Both present serious potential public health problems to large population centers.

Alan D.T. Barrett

Papers

Transmission cycles, host range, evolution and emergence of arboviral disease.

Origin and Evolution of Japanese Encephalitis Virus in Southeast Asia

Guidelines for Plaque-Reduction Neutralization Testing of Human Antibodies to Dengue Viruses

Evolutionary Relationships of Endemic/Epidemic and Sylvatic Dengue Viruses

Yellow Fever: A Disease that Has Yet to be Conquered