RESUMEN

The mechanisms of dengue virus (DENV) pathogenesis are little understood because we have no models of disease; only humans develop symptoms (dengue fever, DF, or dengue hemorrhagic fever, DHF) and research has been limited to studies involving patients. DENV is very diverse: there are four antigenic groups (serotypes) and three to five genetic groups (genotypes) within each serotype. Thus, it has been difficult to evaluate the relative virulence or transmissibility of each DENV genotype; both of these factors are important determinants of epidemiology and their measurement is complex because the natural cycle of this disease involves human-mosquito-human transmission. Although epidemiological and evolutionary studies have pointed to viral factors in determining disease outcome, only recently developed models could prove the importance of specific viral genotypes in causing severe epidemics and their potential to spread to other continents. These new models involve infection of primary human cell cultures, "humanized" mice and field-collected mosquitoes; also, new mathematical models can estimate the impact of viral replication, human immunity and mosquito transmission on epidemic behavior. DENV evolution does not seem to be rapid and the transmission and dispersal of stable, replication-fit genotypes has been more important in the causation of more severe epidemics. Controversy regarding viral determinants of DENV pathogenesis and epidemiology will continue until virulence and transmissibility can be measured under various conditions.

Asunto(s)

Virus del Dengue/inmunología , Virus del Dengue/patogenicidad , Dengue/transmisión , Dengue/virología , Modelos Inmunológicos , Animales , Virus del Dengue/genética , Modelos Animales de Enfermedad , Evolución Molecular , Interacciones Huésped-Patógeno , Humanos , Insectos Vectores/fisiología , Insectos Vectores/virología , Ratones

RESUMEN

Outbreaks of dengue hemorrhagic fever have coincided with the introduction of the Southeast (SE) Asian genotype of dengue type 2 virus in the Western Hemisphere. This introduced genotype appears to be rapidly displacing the indigenous, American genotype of dengue 2 virus throughout the region. These field observations raise the possibility that the SE Asian genotype of dengue 2 is better adapted for vector transmission than its American counterpart. To evaluate this hypothesis, we compared the ability of viral strains of the SE Asian and American genotypes to infect, replicate, and disseminate within vector mosquitoes (Aedes aegypti). Viral strains of the SE Asian genotype tended to infect and disseminate more efficiently in mosquitoes than did variants of the American genotype. These differences, however, were observed solely in field-derived mosquitoes, whereas viral infection rates were virtually identical in the laboratory-adapted Rockefeller colony of Ae. aegypti. Our findings could provide a physiological basis for the contrasting patterns of dengue virus genotype transmission and spread. Such an understanding of functional differences between viral strains and genotypes may ultimately improve surveillance and intervention strategies.

Asunto(s)

Aedes/fisiología , Aedes/virología , Virus del Dengue/genética , Virus del Dengue/fisiología , Insectos Vectores/fisiología , Insectos Vectores/virología , Américas , Animales , Asia , Secuencia de Bases , Virus del Dengue/clasificación , Genes Virales/genética , Genotipo , Factores de Tiempo

RESUMEN

The recent isolation of a nonhuman primate hepadnavirus from woolly monkeys prompted an examination of other primates for potentially new hepadnaviruses. A serological analysis of 30 captive gibbons revealed that 47% were positive for at least one marker of ongoing or previous infection with a hepatitis B virus (HBV). The amino acid sequences of the core and surface genes of human and gibbon virus isolates were very similar. Phylogenetic analysis indicated that the gibbon isolates lie within the human HBV family, indicating that these HBV isolates most likely stem from infection of gibbons from a human source.

Asunto(s)

Infecciones por Hepadnaviridae/veterinaria , Hylobates/virología , Enfermedades de los Monos/virología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , ADN Viral , Hepadnaviridae/clasificación , Hepadnaviridae/genética , Hepadnaviridae/inmunología , Infecciones por Hepadnaviridae/sangre , Infecciones por Hepadnaviridae/inmunología , Infecciones por Hepadnaviridae/virología , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/inmunología , Antígenos del Núcleo de la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Enfermedades de los Monos/sangre , Enfermedades de los Monos/inmunología , Filogenia

RESUMEN

The emergence of epidemic VEE viruses has been reported ever since the virus was first described; this phenomenon is likely to continue to occur because of the high mutation rate of these RNA viruses. A vaccine that was first developed by the US Military for human use has proved helpful in curtailing the spread of VEE virus during epizootics of the disease in equids but not during human epidemics. It has not, however, eliminated the source of these highly pathogenic and transmissible viruses. Occurrences of VEE in equids in Mexico in recent years suggest that the present vaccine is not effective in interrupting transmission of new epizootic viruses arising from what were previously known as avirulent enzootic cycles. Future vaccines against VEE should be based on immunogens derived from enzootic viruses to interrupt VEE virus transmission at the source itself rather than waiting for virulent phenotypes of VEE virus to emerge.

Asunto(s)

Virus de la Encefalitis Equina Venezolana/aislamiento & purificación , Encefalomielitis Equina Venezolana/veterinaria , Enfermedades de los Caballos/epidemiología , Animales , Brotes de Enfermedades/veterinaria , Vectores de Enfermedades , Virus de la Encefalitis Equina Venezolana/clasificación , Virus de la Encefalitis Equina Venezolana/genética , Encefalomielitis Equina Venezolana/epidemiología , Encefalomielitis Equina Venezolana/etiología , Encefalomielitis Equina Venezolana/terapia , Enfermedades de los Caballos/etiología , Enfermedades de los Caballos/terapia , Caballos , Serotipificación

RESUMEN

The understanding of dengue virus pathogenesis has been hampered by the lack of in vitro and in vivo models of disease. The study of viral factors involved in the production of severe dengue, dengue hemorrhagic fever (DHF), versus the more common dengue fever (DF), have been limited to indirect clinical and epidemiologic associations. In an effort to identify viral determinants of DHF, we have developed a method for comparing dengue type 2 genomes (reverse transcriptase PCR in six fragments) directly from patient plasma. Samples for comparison were selected from two previously described dengue type 2 genotypes which had been shown to be the cause of DF or DHF. When full genome sequences of 11 dengue viruses were analyzed, several structural differences were seen consistently between those associated with DF only and those with the potential to cause DHF: a total of six encoded amino acid charge differences were seen in the prM, E, NS4b, and NS5 genes, while sequence differences observed within the 5' nontranslated region (NTR) and 3' NTR were predicted to change RNA secondary structures. We hypothesize that the primary determinants of DHF reside in (i) amino acid 390 of the E protein, which purportedly alters virion binding to host cells; (ii) in the downstream loop (nucleotides 68 to 80) of the 5' NTR, which may be involved in translation initiation; and (iii) in the upstream 300 nucleotides of the 3' NTR, which may regulate viral replication via the formation of replicative intermediates. The significance of four amino acid differences in the nonstructural proteins NS4b and NS5, a presumed transport protein and the viral RNA polymerase, respectively, remains unknown. This new approach to the study of dengue virus genome differences should better reflect the true composition of viral RNA populations in the natural host and permit their association with pathogenesis.

Asunto(s)

Virus del Dengue/genética , Regiones no Traducidas 3'/química , Regiones no Traducidas 5'/química , Secuencia de Aminoácidos , Secuencia de Bases , Virus del Dengue/clasificación , Virus del Dengue/patogenicidad , Genotipo , Humanos , Datos de Secuencia Molecular , Filogenia , ARN Viral/química , Proteínas del Envoltorio Viral/química , Proteínas no Estructurales Virales/química

RESUMEN

Two outbreaks of encephalitis consistent with an etiology of Venezuelan equine encephalitis (VEE) virus occurred in equines on the Pacific coast of southern Mexico in 1993 (Chiapas State) and in 1996 (Oaxaca State). In Chiapas, there were 125 cases, of which 63 were fatal and in Oaxaca, there were 32 cases and 12 fatalities. Virus was isolated from two horses from each outbreak, including three brain isolates and one from blood. Virus isolates (93-42124, ISET-Chi93, Oax131, and Oax142) were shown by indirect immunofluorescence, hemagglutination inhibition, monoclonal antibody ELISA, and nucleotide sequencing to be VEE virus, subtype IE, a type previously thought to be equine-avirulent. Genetic characterization and phylogenetic analysis indicated that the outbreak viruses were identical or nearly identical to one another and that they were closely related to equine-avirulent IE strains from Guatemala and the Gulf coast of Mexico. In a plaque-reduction neutralization test, sera collected from healthy horses in Chiapas and Oaxaca reacted significantly better with isolate 93-42124 than with Guatemala IE isolate 68U201, suggesting that subtle genetic changes may have resulted in alteration of neutralization domains. It is not clear whether these differences may also influence equine virulence. However, renewed VEE virus subtype IE activity in Mexico, and its apparent conversion to equine virulence, underscores the need for increased surveillance, additional laboratory and epidemiologic studies in VEE-endemic regions, and possibly new vaccines.

Asunto(s)

Brotes de Enfermedades/veterinaria , Virus de la Encefalitis Equina Venezolana/clasificación , Encefalomielitis Equina Venezolana/veterinaria , Enfermedades de los Caballos/virología , Secuencia de Aminoácidos , Animales , Animales Recién Nacidos , Anticuerpos Antivirales/sangre , Antígenos Virales/análisis , Virus de la Encefalitis Equina Venezolana/genética , Virus de la Encefalitis Equina Venezolana/inmunología , Encefalomielitis Equina Venezolana/epidemiología , Encefalomielitis Equina Venezolana/virología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Enfermedades de los Caballos/epidemiología , Caballos , Masculino , México/epidemiología , Ratones , Datos de Secuencia Molecular , Pruebas de Neutralización/veterinaria , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , Serotipificación/veterinaria , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/genética

RESUMEN

Hepatitis B virus (HBV) infections are a major worldwide health problem with chronic infections leading to cirrhosis and liver cancer. Viruses related to human HBV have been isolated from birds and rodents, but despite efforts to find hepadnaviruses that infect species intermediate in evolution between rodents and humans, none have been described. We recently isolated a hepadnavirus from a woolly monkey (Lagothrix lagotricha) that was suffering from fulminant hepatitis. Phylogenetic analysis of the nucleotide sequences of the core and surface genes indicated that the virus was distinct from the human HBV family, and because it is basal (ancestral) to the human monophyletic group, it probably represents a progenitor of the human viruses. This virus was designated woolly monkey hepatitis B virus (WMHBV). Analysis of woolly monkey colonies at five zoos indicated that WMHBV infections occurred in most of the animals at the Louisville zoo but not at four other zoos in the United States. The host range of WMHBV was examined by inoculation of one chimpanzee and two black-handed spider monkeys (Ateles geoffroyi), the closest nonendangered relative of the woolly monkey. The data suggest that spider monkeys are susceptible to infection with WMHBV and that minimal replication was observed in a chimpanzee. Thus, we have isolated a hepadnavirus with a host intermediate between humans and rodents and establishes a new animal model for evaluation of antiviral therapies for treating HBV chronic infections.

Asunto(s)

Cebidae/virología , Modelos Animales de Enfermedad , Hepadnaviridae/aislamiento & purificación , Hepatitis B/veterinaria , Hepatitis B/virología , Animales , ADN Viral/química , Genotipo , Hepadnaviridae/genética , Humanos , Datos de Secuencia Molecular , Linaje , Filogenia , Mapeo Restrictivo

RESUMEN

Dengue is a mosquito-borne viral infection that in recent years has become a major international public health concern. Dengue hemorrhagic fever (DHF), first recognized in Southeast Asia in the 1950s, is today a leading cause of childhood death in many countries. The pathogenesis of this illness is poorly understood, mainly because there are no laboratory or animal models of disease. We have studied the genetic relationships of dengue viruses of serotype 2, one of four antigenically distinct dengue virus groups, to determine if viruses obtained from cases of less severe dengue fever (DF) have distinct evolutionary origins from those obtained from DHF cases. A very large number (73) of virus samples from patients with DF or DHF in two locations in Thailand (Bangkok and Kamphaeng Phet) were compared by sequence analysis of 240 nucleotides from the envelope/nonstructural protein 1 (E/NS1) gene junction of the viral genome. Phylogenetic trees generated with these data have been shown to reflect long-term evolutionary relationships among strains. The results suggest that 1) many different virus variants may circulate simultaneously in Thailand, thus reflecting the quasispecies nature of these RNA viruses, in spite of population immunity; 2) viruses belonging to two previously distinct genotypic groups have been isolated from both DF and DHF cases, supporting the view that they arose from a common progenitor and share the potential to cause severe disease; and 3) viruses associated with the potential to cause DHF segregate into what is now one, large genotypic group and they have evolved independently in Southeast Asia for some time.

Asunto(s)

Virus del Dengue/genética , ARN Viral/análisis , Dengue Grave/genética , Proteínas del Envoltorio Viral/genética , Proteínas no Estructurales Virales/genética , Dengue/epidemiología , Dengue/genética , Virus del Dengue/patogenicidad , Evolución Molecular , Humanos , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , ARN Viral/genética , Alineación de Secuencia , Análisis de Secuencia de ARN , Homología de Secuencia de Ácido Nucleico , Dengue Grave/epidemiología , Tailandia/epidemiología , Virulencia/genética

RESUMEN

Due to the increasing severity of hemorrhagic dengue epidemics during the last years in Venezuela, a retrospective analysis was conducted to identify the behaviour of the dengue virus serotypes circulating in the country and the molecular evolution of dengue virus serotype 2. The data presented here indicates that dengue virus serotypes 1, 2 and 4 are endemic in Venezuela, they circulate simultaneously around the year in the biggest urban cities, however, one particular serotype is predominant during an epidemic period and replaces the virus serotype dominant during the previous epidemic period. The increased severity of dengue fever since 1989 in Venezuela might be associated to the introduction of the Asiatic genotype of virus which replaced the autochthonous Caribbean genotype. The Asiatic genotype is recognised as a more virulent virus.

Asunto(s)

Virus del Dengue/clasificación , Virus del Dengue/genética , Dengue/epidemiología , Dengue/virología , Virus del Dengue/aislamiento & purificación , Evolución Molecular , Genotipo , Humanos , Incidencia , Pruebas de Mutagenicidad , Estudios Retrospectivos , Serotipificación , Venezuela/epidemiología

RESUMEN

Venezuelan equine encephalitis (VEE) epidemics and equine epizootics occurred periodically in the Americas from the 1920s until the early 1970s, when the causative viruses, subtypes IAB and IC, were postulated to have become extinct. Recent outbreaks in Columbia and Venezuela have renewed interest in the source of epidemic/epizootic viruses and their mechanism of interepizootic maintenance. We performed phylogenetic analyses of VEE virus isolates spanning the entire temporal and geographic range of strains available, using 857-nucleotide reverse transcription-PCR products including the E3 and E2 genes. Analyses indicated that epidemic/epizootic viruses are closely related to four distinct, enzootic subtype ID-like lineages. One of these lineages, which occurs in Columbia, Peru, and Venezuela, also included all of the epidemic/epizootic isolates; the remaining three ID-like lineages, which occur in Panama, Peru, Florida, coastal Ecuador, and southwestern Columbia, were apparently not associated with epizootic VEE emergence. Within the Columbia/Peru/Venezuela lineage, three distinct monophyletic groups of epidemic/epizootic viruses were delineated, indicating that VEE emergence has occurred independently at least three times (convergent evolution). Representative, complete E2 amino acid sequences were compared to identify potential determinants of equine virulence and epizootic emergence. Amino acids implicated previously in laboratory mouse attenuation generally did not vary among the natural isolates that we examined, indicating that they probably are not involved in equine virulence changes associated with VEE emergence. Most informative amino acids correlated with phylogenetic relationships rather than phenotypic characteristics, suggesting that VEE emergence has resulted from several distinct combinations of mutations that generate viruses with similar antigenic and equine virulence phenotypes.

Asunto(s)

Virus de la Encefalitis Equina Venezolana/genética , Encefalomielitis Equina Venezolana/epidemiología , Encefalomielitis Equina Venezolana/virología , Secuencia de Aminoácidos , Secuencia de Bases , Evolución Biológica , ADN Viral , Brotes de Enfermedades , Virus de la Encefalitis Equina Venezolana/clasificación , Genotipo , Datos de Secuencia Molecular , Filogenia , Homología de Secuencia de Aminoácido , Proteínas del Envoltorio Viral/genética

RESUMEN

The recent emergence and spread of dengue hemorrhagic fever in the Americas have been a major source of concern. Efforts to control this disease are dependent on understanding the pathogenicity of dengue viruses and their transmission dynamics. Pathogenicity studies have been hampered by the lack of in vitro or in vivo models of severe dengue disease. Alternatively, molecular epidemiologic studies which associate certain dengue virus genetic types with severe dengue outbreaks may point to strains with increased pathogenicity. The comparison of nucleotide sequences (240 bp) from the E/NS1 gene region of the dengue virus genome has been shown to reflect evolutionary relationships and geographic origins of dengue virus strains. This approach was used to demonstrate an association between the introduction of two distinct genotypes of dengue type 2 virus and the appearance of dengue hemorrhagic fever in the Americas. Phylogenetic analyses suggest that these genotypes originated in Southeast Asia and that they displaced the native, American genotype in at least four countries. Vaccination and other control efforts should therefore be directed at decreasing the transmission of these "virulent" genotypes.

Asunto(s)

Virus del Dengue/clasificación , Virus del Dengue/patogenicidad , Dengue/virología , Secuencia de Bases , Brasil , Colombia , ADN Viral , Virus del Dengue/genética , Genotipo , Humanos , México , Datos de Secuencia Molecular , Filogenia , Venezuela , Proteínas del Envoltorio Viral/genética , Proteínas no Estructurales Virales/genética

RESUMEN

BACKGROUND: Venezuelan equine encephalomyelitis (VEE) virus has caused periodic epidemics among human beings and equines in Latin America from the 1920s to the early 1970s. The first major outbreak since 1973 occurred in Venezuela and Colombia during 1995, and involved an estimated 75,000 to 100,000 people. We report an epidemiological and virological investigation of this epidemic. METHODS: Virus isolates were made in cell culture from human serum, human throat swabs, and brain tissue from aborted and stillborn human fetuses, as well as from horse brain tissue and pooled mosquito collections. Human sera were also tested for VEE-specific antibodies. The serotypes of VEE isolates were identified by antigen assays, and viruses were characterised genetically by sequencing PCR products generated from the E3 and E2 genes. Phylogenetic analyses were done to determine evolutionary relations with respect to previous epidemic/epizootic and enzootic VEE virus isolates. Mosquito collections were made to identify possible vectors, and clinical findings were determined by direct observation of patients visiting hospitals and clinics in affected regions, and by inspecting patient records. Equine vaccination and vector control were used in an attempt to halt the spread of the outbreak. FINDINGS: Most affected people had an acute, self-limited febrile illness of 3 to 4 days duration. However, convulsions were often seen in children, and abortions and fetal deaths occurred in pregnant women infected with VEE virus. Antigenic characterisation of 12 virus isolates spanning the temporal and spatial range of the outbreak indicated that all are VEE serotype IC. Phylogenetic analysis revealed that all of the 1995 viruses were closely related to serotype IC viruses isolated during a large VEE outbreak that occurred in the same regions of Colombia and Venezuela from 1962-1964. A 1983 mosquito isolate from north central Venezuela was also closely related to the 1995 isolates. INTERPRETATION: This outbreak was remarkably similar to one that occurred in same regions of Venezuela and Colombia during 1962-1964. Symptoms of infected patients, estimated mortality rates, meteorological conditions preceding the epidemic, and seasonal patterns of transmission were all very similar to those reported in the previous outbreak. In addition, viruses isolated during 1995 were antigenically and genetically nearly identifical to those obtained during 1962-1964. These findings suggest that the epidemic resulted from the re-emergence of an epizootic serotype IC VEE virus. Identification of a similar virus isolate in mosquitoes in Venezuela in 1983, 10 years after epidemic/epizootic VEE activity ceased, raises the possibility of a serotype IC enzootic transmission cycle in northern Venezuela.

Asunto(s)

Brotes de Enfermedades , Encefalomielitis Equina Venezolana/epidemiología , Adolescente , Adulto , Animales , Niño , Preescolar , Colombia/epidemiología , Brotes de Enfermedades/veterinaria , Virus de la Encefalitis Equina Venezolana/clasificación , Virus de la Encefalitis Equina Venezolana/aislamiento & purificación , Encefalomielitis Equina Venezolana/veterinaria , Encefalomielitis Equina Venezolana/virología , Femenino , Enfermedades de los Caballos/epidemiología , Caballos , Humanos , Lactante , Persona de Mediana Edad , Datos de Secuencia Molecular , Embarazo , Venezuela/epidemiología

RESUMEN

Sabiá virus, one of five arenaviruses from South America known to cause hemorrhagic fever in humans, emerged in 1990 when it was isolated from a fatal case in Sao Paulo, Brazil. Subsequently, it has caused two laboratory-acquired infections. Its natural distribution and host are still unknown. Using viral RNA and multiple polymerase chain reaction products as templates, the nucleotide sequence of the small (S) RNA segment of Sabiá virus, which codes for the nucleocapsid (N) and glycoprotein precursor, was determined. This virus shares an ambisense genome in common with other arenaviruses, although it has a unique predicted three stem--loop structure in the S RNA intergenic region. Phylogenetic analysis of a portion of the N gene sequence confirmed that Sabiá virus is distinct from all other members of the Arenaviridae and shares a progenitor with Junin, Machupo, Tacaribe, and Guanarito viruses.

Asunto(s)

Arenavirus del Nuevo Mundo/clasificación , Arenavirus del Nuevo Mundo/genética , Fiebre Hemorrágica Americana/virología , Secuencia de Aminoácidos , Animales , Arenavirus del Nuevo Mundo/aislamiento & purificación , Secuencia de Bases , Brasil , Cápside/genética , Chlorocebus aethiops , ADN Viral , Humanos , Ratones , Datos de Secuencia Molecular , Conformación de Ácido Nucleico , Filogenia , Precursores de Proteínas/genética , ARN Viral , Homología de Secuencia de Aminoácido , Células Vero , Proteínas del Núcleo Viral/genética

RESUMEN

The nucleotide sequence of a portion of the nucleocapsid (N) gene of the Guanarito virus prototype strain (INH-95551) has been determined. It was obtained by direct RNA and polymerase chain reaction (PCR) fragment sequencing of the 3' end of the small (S) RNA fragment. A comparison of this 782-nucleotide segment was done with the known homologous gene sequences of five other arenaviruses: Junin, Machupo, Tacaribe, Pichinde, and lymphocytic choriomeningitis (LCM). Phylogenetic analysis of the N gene open reading frame showed that Guanarito virus is genetically distinct from other members of the Arenavirus family, with 32% nucleotide sequence divergence from Junin, 30% from Machupo, 32% from Tacaribe, 41% from Pichinde, and 45% from LCM. Comparison of amino acids encoded by this sequence region indicated a probable antigenic domain (amino acids 55-63) shared among all arenaviruses studied to date. Along with its host restriction and focal distribution, our data support the hypothesis that this virus has been evolving independently in its endemic focus, for some time.

Asunto(s)

Infecciones por Arenaviridae/virología , Arenavirus/genética , Secuencia de Aminoácidos , Arenavirus/clasificación , Arenavirus/inmunología , Secuencia de Bases , Cápside/química , Cápside/genética , Cápside/inmunología , Cartilla de ADN/química , Epítopos/inmunología , Genes Virales/genética , Humanos , Virus de la Coriomeningitis Linfocítica/genética , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa , ARN Viral/análisis , ARN Viral/química , ARN Viral/aislamiento & purificación , Homología de Secuencia de Aminoácido , Proteínas del Núcleo Viral/química , Proteínas del Núcleo Viral/genética , Proteínas del Núcleo Viral/inmunología

RESUMEN

One of the most important questions in arbovirology concerns the origin of epidemic Venezuelan equine encephalitis (VEE) viruses; these viruses caused periodic, extensive epidemics/epizootics in the Americas from 1938-1973 (reaching the United States in 1971) but had recently been presumed extinct. We have documented the 1992 emergence of a new epidemic/epizootic VEE virus in Venezuela. Phylogenetic analysis of strains isolated during two outbreaks indicated that the new epidemic/epizootic virus(es) evolved recently from an enzootic VEE virus in northern South America. These results suggest continued emergence of epizootic VEE viruses; surveillance of enzootic viruses and routine vaccination of equines should therefore be resumed.

Asunto(s)

Virus de la Encefalitis Equina Venezolana/clasificación , Encefalomielitis Equina Venezolana/virología , Animales , Evolución Biológica , Virus de la Encefalitis Equina Venezolana/genética , Virus de la Encefalitis Equina Venezolana/aislamiento & purificación , Encefalomielitis Equina Venezolana/epidemiología , Encefalomielitis Equina Venezolana/veterinaria , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/virología , Caballos , Humanos , Datos de Secuencia Molecular , Filogenia , América del Sur , Especificidad de la Especie , Venezuela/epidemiología

RESUMEN

We studied the evolution of alphaviruses in the Venezuelan equine encephalitis (VEE) complex using phylogenetic analysis of RNA nucleotide sequences from limited portions of the nsP4, E1, and 3' untranslated genome regions of representative strains. The VEE complex constituted a monophyletic group of viruses (descended from a common ancestor); some serologic VEE varieties such as subtype III formed monophyletic groups while subtype I did not. Subtype II Everglades and variety ID enzootic viruses formed a monophyletic group which also included all epizootic variety IAB and IC VEE isolates. Everglades virus diverged from this ID lineage (colonized North America) ca. 100-150 years ago, followed by divergence of variety IAB and IC epizootic viruses. Variety IAB viruses probably emerged from the variety ID lineage once during the early part of this century, while variety IC viruses evolved at least two times. These results identify the source of epizootic VEE viruses as the variety ID enzootic virus lineage which occurs in northern South America and Panama. Even if variety IAB and IC viruses are extinct, recent, multiple emergences of epizootic viruses from an enzootic lineage suggests that other epizootic VEE viruses may evolve again in the future. The close genetic relationship of subtype II Everglades virus to the variety ID lineage also implies the potential for emergence of equine-virulent VEE viruses in Florida.

Asunto(s)

Virus de la Encefalitis Equina Venezolana/clasificación , Secuencia de Bases , Evolución Biológica , ADN Viral , Virus de la Encefalitis Equina Venezolana/genética , Datos de Secuencia Molecular , Mutación , Fenotipo , Filogenia , ARN Viral/análisis , Homología de Secuencia de Ácido Nucleico

RESUMEN

Primer-extension sequencing of the RNA template of polio, dengue, Rift Valley fever, and Japanese encephalitis (JE) viruses has provided new information on their geographic distribution, origin, and evolution. In a previous study of 46 diverse JE virus strains, we demonstrated the existence of three distinct JE genotypes in Asia. We now report the occurrence of a fourth genotype. In the present study, 19 JE virus isolates, representing various geographic regions of Asia and a 50-year time span, were compared with each other and with Murray Valley encephalitis, West Nile, and Kunjin viruses. Twelve of the JE strains from the Indonesian Archipelago and the Philippines had not been previously examined; the remainder were representatives of the three previously identified genotypes. Two hundred forty nucleotides from the pre-M gene region of the virus were used in these comparisons. Using 12% divergence as a cut-off point, the 19 JE strains fell into four distinct genotypic groups; maximum divergence across the comparison region was 21%. The newly recognized fourth genotype was comprised of five Indonesian isolates that were 7% divergent from the rest of the JE viruses.

Asunto(s)

Virus de la Encefalitis Japonesa (Especie)/genética , Precursores de Proteínas/química , ARN Viral/química , Proteínas de la Matriz Viral/química , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Virus de la Encefalitis Japonesa (Especie)/clasificación , Flavivirus/clasificación , Flavivirus/genética , Genotipo , Humanos , Indonesia , Datos de Secuencia Molecular , Precursores de Proteínas/genética , Proteínas de la Matriz Viral/genética

Asunto(s)

Alphavirus/genética , Animales , Evolución Biológica , Variación Genética , Humanos , Infecciones por Togaviridae/microbiología , Infecciones por Togaviridae/transmisión

RESUMEN

An outbreak of severe haemorrhagic illness began in the municipality of Guanarito, Portuguesa State, Venezuela, in September, 1989. Subsequent detailed study of 15 cases confirmed the presence of a new viral disease, designated Venezuelan haemorrhagic fever. Characteristic features are fever, toxicity, headache, arthralgia, diarrhoea, conjunctivitis, pharyngitis, leucopenia, thrombocytopenia, and haemorrhagic manifestations. Other features include facial oedema, cervical lymphadenopathy, nausea/vomiting, cough, chest or abdominal pain, and convulsions. The patients ranged in age from 6 to 54 years; all were residents of rural areas in central Venezuela, and 9 died. Infection with Guanarito virus, a newly recognised arenavirus, was shown by direct culture or by serological confirmation in all cases. Epidemiological studies suggest that the disease is endemic in some rural areas of central Venezuela and that it is rodent-borne. Venezuelan haemorrhagic fever has many similarities to Lassa fever and to the arenavirus haemorrhagic fevers that occur in Argentina and Bolivia.

Asunto(s)

Brotes de Enfermedades , Fiebre Hemorrágica Americana/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Animales , Animales Salvajes/microbiología , Arenavirus del Nuevo Mundo/aislamiento & purificación , Niño , Femenino , Fiebre Hemorrágica Americana/complicaciones , Fiebre Hemorrágica Americana/transmisión , Humanos , Masculino , Persona de Mediana Edad , Roedores/microbiología , Salud Rural , Venezuela/epidemiología

RESUMEN

We examined the rate and spatial pattern of eastern equine encephalomyelitis virus (EEEV) evolution in North America using primer-extension sequencing of viral RNA. Nucleotide sequences of the entire 26 S structural gene region of four EEEV strains revealed remarkable conservation between 1933 and 1985, with an estimated 0.7% divergence or 1.4 x 10(-4) nucleotide substitutions per site per year. Sequences from smaller 26 S regions of nine additional strains suggested that EEEV evolves in North America in a single lineage, with genetic exchange regularly occurring among enzootic transmission foci. In these limited 26 S genome regions, only synonymous nucleotide substitutions became fixed between 1933 and 1988, implying a high degree of conservation in protein structure. Short nucleotide sequences from a Panamanian, South American variety isolate revealed a relatively distant relationship to North American serotype viruses. This suggested genetic divergence between antigenic varieties, and independent evolution of EEEV in North and South America. Factors related to replication and epidemiology of EEEV, which may constrain its evolution in nature, are discussed. Possible mechanisms of genetic exchange among enzootic foci are also considered.

Asunto(s)

Virus de la Encefalitis Equina del Este/genética , Genes Virales , ARN Viral/genética , Proteínas Estructurales Virales/genética , Secuencia de Aminoácidos , Secuencia de Bases , Evolución Biológica , Cápside/genética , Glicoproteínas de Membrana/genética , Datos de Secuencia Molecular , América del Norte