
Full text loading...
Category: Viruses and Viral Pathogenesis
Alphaviruses, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815981/9781555814250_Chap54-1.gif /docserver/preview/fulltext/10.1128/9781555815981/9781555814250_Chap54-2.gifAbstract:
The alphaviruses are principally mosquito-borne, positive-strand RNA viruses in the family Togaviridae that exhibit a broad range of pathogenicity in humans and animals. The replication complexes of alphaviruses are associated with cytoplasmic membranes, and the main determinant of membrane attachment seems to be nsP1, which is hydrophobically modified by palmitoylation of cysteine residues. In humans, an age-dependent susceptibility of infants and the elderly to central nervous system (CNS) infection has been observed epidemiologically, although its pathogenesis has not been elucidated. Immature mouse neurons infected with Sindbis Virus (SINV) or Semliki Forest Virus (SFV) die of caspase-dependent apoptosis, while mature neurons survive by producing factors inhibiting virus-induced apoptosis. Apoptosis is induced at the time of alphavirus fusion with the cell membrane, and virus replication is not required. Mayaro virus (MAYV) is the principal New World representative of alphaviruses within the SFV complex. The epidemiological pattern is explained by the forest cycle of viral transmission, probably between Hemagogus mosquitoes and wild vertebrates, including monkeys and marmosets, analogous to the sylvatic cycle of yellow fever. The majority of infections with the arthritogenic alphaviruses are benign but temporarily debilitating. Barmah Forest virus (BFV), named after the site in northern Victoria where it was first isolated from Culex annulirostris mosquitoes, is antigenically distinct from other alphaviruses, including River virus (RRV) and SINV, that are also found in Australia. Alphaviruses principally are maintained in zoonotic transmission cycles in natural habitats.
Full text loading...
Genetic relationship of alphavirus species and some major subtypes (shown in parentheses) based on partial sequences of E1 glycoprotein gene. The main antigenic complexes are indicated on the right. The dotted line represents the recombination event between SINV and EEEV. Numbers on the lines indicate bootstrap values for clades to the right using the neighbor-joining (numbers above branches) or Bayesian (numbers below line) method. (Reprinted from reference 49 with permission.)
RRV. (Left) Cryoelectron microscopic image reconstruction of RRV showing the flower-like envelope protein spikes, virion membrane, and nucleocapsid core. (Right) Relationships of spike and capsid proteins and virion RNA. (Courtesy of R. J. Kuhn.)
Schematic diagram of alphavirus genome [positive (⊕) sense RNA with poly(A) (An) tail and 5′ terminal cap (CAP); viral complementary RNA (vcRNA) of negative (⊖) sense; and subgenomic mRNA of positive sense]. Viral nonstructural proteins are translated from the 5′ two-thirds region of the genome, yielding polyprotein intermediates and nonstructural proteins nsP1 to nsP4. RNA is replicated into negative-sense RNA templates and transcribed into 26S subgenomic RNA. Cotranslational processing of the subgenomic mRNA yields the three principal structural proteins: capsid and envelope glycoproteins (E1 and E2). ORF, open reading frame; nt, nucleotide.
After binding to the cell membrane (step 1), virions are taken up in endocytic vesicles (steps 2 and 3). The virion and vesicular membranes fuse, releasing the nucleocapsid (step 4). The viral nucleocapsid binds to a ribosome (step 5) and is uncoated, freeing viral RNA (step 6) from the individual capsid (gray dots). Positive-sense viral RNA (heavy line) is replicated (step 7), producing complementary negative-sense RNA (gray line) (step 8), which in turn is transcribed to full-length genomic positive-sense RNA (step 9) or subgenomic RNA (step 10). Nonstructural proteins (nsp) are translated from genomic RNA. Subgenomic RNA is translated to produce capsid proteins (black dots) and envelope proteins, which are modified before insertion into the cell membrane (gray bars) (step 11). Genomic RNA is packaged with capsid proteins into nucleocapsid cores (step 12); capsid and E2 proteins associate (step 13) prior to viral budding (step 14).
Reported cases of EEE among humans in the United States, 1964 to 2006. The reported incidence is highest in Florida, where equine cases are reported perennially from the northeastern coast and throughout the peninsula. Relatively constant inland foci of transmission have been identified in upstate New York, southwestern Michigan, northeastern Indiana, and southcentral Georgia. In Massachusetts, human cases have been reported almost entirely from the eastern counties and in New Jersey from the southern counties. (Reprinted from the Centers for Disease Control and Prevention at http://www.cdc.gov/ncidod/dvbid/arbor/arbocase.htm.)
Reported cases of EEE (broken line) and WEE (solid line), United States, 1964 to 2006. (Reprinted from the Centers for Disease Control and Prevention at http://www.cdc.gov/ncidod/dvbid/arbor/arbocase.htm.)
Schematic diagram of the EEE transmission cycle; solid lines show known portions, and broken lines show speculative portions. The principal enzootic mosquito vector, Culiseta melanura, transmits the virus among birds and occasionally initiates an outbreak among pheasants or other captive birds. Various other species bridge the enzootic cycle to infect humans and horses, which are dead-end hosts; the principal species include Aedes sollicitans, found in salt marsh coastal habitat; Aedes vexans, associated with open meadows and flooded ground pools; Aedes canadensis, associated with woodland pools; and Coquillettidia perturbans, found in open freshwater swamps with emerging vegetation. The viral overwintering mechanism is unknown but potentially includes vertically infected mosquitoes, persistently infected birds, and other vertebrates.
Reported cases of EEE and WEE by month, United States, 1972 to 1989. (Data from the Centers for Disease Control and Prevention at http://www.cdc.gov/ncidod/dvbid/arbor/arbocase.htm.)
Reported cases of WEE among humans in the United States, 1964 to 2006. (Reprinted from the Centers for Disease Control and Prevention at http://www.cdc.gov/ncidod/dvbid/arbor/arbocase.htm.)
Geographic distribution of VEE epizootics and sylvatic viral subtypes.
(A) Sylvatic VEEVs circulate continuously in silent tropical and subtropical foci among Culex melaconion mosquitoes and small mammals or aquatic birds. Humans (e.g., soldiers on jungle bivouacs) are infected when they chance upon transmission foci. Bridging vectors (e.g., Aedes taeniorhychus) that feed on viremic vertebrates in a sylvatic focus can carry the virus to nearby areas of human activity. (B) In contrast to the continuous cycling of sylvatic VEEV subtypes, until recently, epizootic VEEV had never been isolated except during periodic outbreaks. Once introduced, epizootic viruses are rapidly amplified among equines (horses and burros). Equines develop high viremia levels, so various mosquito species can function as biological vectors (only some important species are shown) and other biting insects, such as blackflies, can spread the virus mechanically. Humans develop illness with high viremia levels but probably have an insignificant role, if any, in viral amplification. Transmission declines as susceptible equines are exhausted by natural infection or immunization. It is speculated that epizootic IC viruses arise by mutation from sylvatic ID viruses; the subpopulation circulates in a sylvatic cycle and under appropriate conditions is amplified, leading to epizootic and epidemic spread.
Reported chikungunya epidemics by year.
Small papular lesions seen in Sindbis (Ockelbo) fever. (Courtesy of B. Niklasson.)
Notifications and notification rates of RRV infections, Australia, 2005–2006, by Statistical Division of residence. (Reprinted from reference 81 with permission.)
Crude annual rate of BFV and RRV infection notifications, Australia, 1 July 1991 to 30 June 2006, by season of onset. (Reprinted from reference 81 with permission.)
Selected characteristics of alphaviruses a
Alphavirus proteins
Initial diagnosis of diseases ultimately proven by laboratory test to be either WEE or St. Louis encephalitis a
Precautions to minimize exposure to mosquitoes and ticks a