RESUMO
We examined human herpesvirus 8 (HHV-8) seroprevalence and seroincidence among 245 homosexual men from New York City (NYC) and Washington, DC (DC) who have been followed since 1982. An immunofluorescence assay measured antibodies to a latent HHV-8 nuclear antigen. Seroprevalence was 20.4% in 1982; seroincidence was approximately 15%/year during 1982-1983 but fell sharply thereafter. NYC men had a higher seroprevalence (odds ratio, 3.43; P<.001) and seroincidence (rate ratio, 2.13; P=.01) than DC men. Risk of Kaposi's sarcoma (KS) was increased in seropositive men (adjusted relative hazard, 3.58; P=.02). Among men who were seropositive for both human immunodeficiency virus type 1 and HHV-8, the 10-year cumulative risk of KS was 39%; time from coinfection to KS diagnosis ranged from 15 to 154 months (median, 63.5 months). This study shows an epidemic of HHV-8 among US homosexual men in the early 1980s that was associated with a high risk of developing KS.
Assuntos
Infecções por HIV/epidemiologia , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 8 , Homossexualidade Masculina/estatística & dados numéricos , Sarcoma de Kaposi/epidemiologia , Anticorpos Antivirais/sangue , Comorbidade , District of Columbia , Seguimentos , Infecções por HIV/imunologia , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/imunologia , HIV-1 , Infecções por Herpesviridae/imunologia , Humanos , Incidência , Masculino , Cidade de Nova Iorque/epidemiologia , Razão de Chances , Prevalência , Fatores de Risco , Sarcoma de Kaposi/imunologia , Fatores de TempoRESUMO
In addition to the major surface (S) protein, the envelope of the duck hepatitis B virus (DHBV) contains a related presurface (preS) protein whose N-terminus bears a covalently attached myristate group. We have explored the functional significance of this modification by examining the replicative potential of a mutant viral genome whose myristylation signal has been inactivated. Following transfection into permissive hepatoma cells, the mutant expresses an unmyristylated preS protein of normal size, immunoreactivity and stability. Cytoplasmic cores containing viral DNA are synthesized, and Dane particles are assembled and exported into the medium. However, the mutant is noninfectious when inoculated into susceptible ducklings. We conclude that myristylation of preS proteins is essential for hepadnaviral infectivity but not for viral assembly; myristylation is most likely required for an early step of the life cycle involving the entry or uncoating of virus particles.
Assuntos
Genes Virais , Vírus da Hepatite B do Pato/fisiologia , Ácidos Mirísticos/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas do Envelope Viral/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Células Cultivadas , Códon/genética , Vírus da Hepatite B do Pato/genética , Vírus da Hepatite B do Pato/patogenicidade , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Ácido Mirístico , Sondas de Oligonucleotídeos , TransfecçãoRESUMO
To investigate the mechanism by which complex membrane proteins achieve their correct transmembrane orientation, we examined in detail the hepatitis B surface antigen for sequences which determine its membrane topology. The results demonstrated the presence of at least two kinds of topogenic elements: an N-terminal uncleaved signal sequence and an internal element containing both signal and stop-transfer function. Fusion of reporter groups to either end of the protein suggested that both termini are translocated across the membrane bilayer. We propose that this topology is generated by the conjoint action of both elements and involves a specifically oriented membrane insertion event mediated by the internal sequence. The functional properties of each element can be instructively compared with those of simpler membrane proteins and may provide insight into the generation of other complex protein topologies.
Assuntos
Antígenos de Superfície da Hepatite B , Proteínas de Membrana , Transporte Biológico , Análise Mutacional de DNA , Globinas/genética , Antígenos de Superfície da Hepatite B/genética , Microssomos/metabolismo , Conformação Proteica , Sinais Direcionadores de Proteínas , Proteínas Recombinantes de Fusão , Relação Estrutura-AtividadeAssuntos
Plexo Corióideo/ultraestrutura , Fosfatase Alcalina/análise , Animais , Bovinos , Fracionamento Celular/métodos , Membrana Celular/enzimologia , Membrana Celular/ultraestrutura , Centrifugação com Gradiente de Concentração/métodos , Plexo Corióideo/enzimologia , Coloides , Dióxido de Silício , ATPase Trocadora de Sódio-Potássio/análise , gama-Glutamiltransferase/análiseRESUMO
The rapid kinetics of D-glucose uptake into membrane vesicles, prepared from the renal cortex of the rat, were measured. A vacuum manifold apparatus for the filtration of suspensions containing membrane vesicles and radiolabelled sugars was constructed to permit measurements of D-glucose accumulation within the vesicles at 8-s intervals. The rate of Na+-independent accumulation of D-glucose was nearly constant for the first 24 s while the rate for Na+-dependent uptake was always changing. While a linear relationship between Na+-dependent D-glucose accumulation and time could not be established for a time period as short as 8 s, the time for half maximum Na+-dependent D-glucose uptake could be estimated. A value of 4 s for half maximum accumulation D-glucose into membrane vesicles in the presence of sodium was obtained.