RESUMEN
HIV-2 is thought to have entered the human population in the 1930s through cross-species transmission of SIV from sooty mangabeys in West Africa. Unlike HIV-1, HIV-2 has not led to a global pandemic, and recent data suggest that HIV-2 prevalence is declining in some West African states where it was formerly endemic. Although many early isolates of HIV-2 were derived from patients presenting with AIDS-defining illnesses, it was noted that a much larger proportion of HIV-2-infected subjects behaved as long-term non-progressors (LTNP) than their HIV-1-infected counterparts. Many HIV-2-infected adults are asymptomatic, maintaining an undetectable viral load for over a decade. However, despite lower viral loads, HIV-2 progresses to clinical AIDS without therapeutic intervention in most patients. In addition, successful treatment with anti-retroviral therapy (ART) is more challenging than for HIV-1. HIV-2 is significantly more sensitive to restriction by host restriction factor tripartite motif TRIM5α than HIV-1, and this difference in sensitivity is linked to differences in capsid structure. In this review we discuss the determinants of HIV-2 disease progression and focus on the important interactions between TRIM5α and HIV-2 capsid in long-term viral control.
Asunto(s)
Proteínas de la Cápside/metabolismo , Infecciones por VIH/epidemiología , VIH-1/fisiología , VIH-2/fisiología , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Adulto , África Occidental/epidemiología , Animales , Factores de Restricción Antivirales , Enfermedades Asintomáticas , Proteínas de la Cápside/genética , Cercocebus atys , Progresión de la Enfermedad , Enfermedades Endémicas , Infecciones por VIH/mortalidad , Humanos , Análisis de Supervivencia , Proteínas de Motivos Tripartitos/genética , Ubiquitina-Proteína Ligasas/genética , Factores de VirulenciaRESUMEN
BACKGROUND: Pain is recognised to have both a sensory dimension (intensity) and an affective dimension (unpleasantness). Pain feels like a single unpleasant bodily experience, but investigations of human pain have long considered these two dimensions of pain to be separable and differentially modifiable. The evidence underpinning this separability and differential modifiability is seldom presented. We aimed to fill this gap by evaluating the current evidence base for whether or not the sensory and affective dimensions of pain can be selectively modulated using cognitive manipulations. METHODS: A rigorous systematic search, based on a priori search terms and consultation with field experts, yielded 4270 articles. A detailed screening process was based on the following recommendations: (i) evaluation of effectiveness; (ii) examination of methodological rigour, including each study having an a priori intention to cognitively modulate one of the two dimensions of pain; and (iii) sound theoretical reasoning. These were used to ensure that included studies definitively answered the research question. RESULTS: After in-depth critique of all 12 articles that met the inclusion criteria, we found that there is no compelling evidence that the sensory and affective dimensions of pain can be selectively and intentionally modulated using cognitive manipulations in humans. CONCLUSIONS: We offer potential explanations for this discrepancy between assumptions and evidence and contend that this finding highlights several important questions for the field, from both the research and clinical perspectives.
Asunto(s)
Afecto , Terapias Mente-Cuerpo/métodos , Dimensión del Dolor/métodos , Percepción del Dolor , Dolor/fisiopatología , Dolor/psicología , HumanosRESUMEN
KIR3DS1*0130111 differs from KIR3DS1*0130101 with two previously undescribed single nucleotide polymorphisms.
Asunto(s)
Alelos , Exones , Polimorfismo de Nucleótido Simple , Receptores KIR3DL1/genética , Receptores KIR3DS1/genética , Sustitución de Aminoácidos , Secuencia de Bases , Genotipo , Humanos , Datos de Secuencia Molecular , Tipificación Molecular , Reacción en Cadena de la Polimerasa , Receptores KIR3DL1/inmunología , Receptores KIR3DS1/inmunología , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
KIR3DL1*0250102 differs from the common West African KIR3DL1*0150101 by 11 single nucleotide polymorphisms (SNPs).
Asunto(s)
Receptores KIR3DL1/genética , África Occidental , Alelos , Humanos , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Receptores KIR3DL1/químicaRESUMEN
KIR3DL1*087 is significantly different from KIR3DL1*0010101 with multiple non-synonymous changes and insertion/deletion sites.
Asunto(s)
Alelos , Receptores KIR3DL1/química , Receptores KIR3DL1/genética , Análisis de Secuencia de ADN/métodos , Secuencia de Bases , Humanos , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Alineación de SecuenciaRESUMEN
The full length sequence of KIR3DL1*0250103 differs from that of KIR3DL1*0150101 with nine single-nucleotide polymorphisms.
Asunto(s)
Alelos , Polimorfismo de Nucleótido Simple , Receptores KIR3DL1/genética , África Occidental , Secuencia de Bases , Exones , Genotipo , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Intrones , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Receptores KIR3DL1/inmunología , Análisis de Secuencia de ADN , Donantes de TejidosRESUMEN
KIR3DL1*0150210 has seven point mutations compared to the common Asian allele KIR3DL1*0150201.
Asunto(s)
Alelos , Mutación Puntual , Receptores KIR3DL1/genética , Recombinación Genética , Secuencia de Bases , Exones , Genotipo , Humanos , Datos de Secuencia Molecular , Tipificación Molecular , Receptores KIR3DL1/inmunología , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
KIR3DL1*0310102 differs from KIR3DL1*0150101 with 11 nucleotide substitutions.
Asunto(s)
Alelos , Mutación Puntual , Receptores KIR3DL1/genética , África Occidental , Secuencia de Bases , Exones , Genotipo , Humanos , Intrones , Datos de Secuencia Molecular , Tipificación Molecular , Receptores KIR3DL1/inmunología , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
KIR3DL1*0040102 allele differs from KIR3DL1*0040101 by a single-nucleotide change at position 12356 (intron 6).
Asunto(s)
Población Negra/genética , Receptores KIR3DL1/química , Receptores KIR3DL1/genética , Donantes de Tejidos , Humanos , Intrones/genética , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Receptores KIR3DL1/aislamiento & purificación , Alineación de SecuenciaRESUMEN
Full-length sequences of KIR3DL1*0150209 differ from those of KIR3DL1*0150201 with seven single-nucleotide polymorphisms.
Asunto(s)
Alelos , Polimorfismo de Nucleótido Simple , Receptores KIR3DL1/genética , Pueblo Asiatico , Secuencia de Bases , Genotipo , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Intrones , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Receptores KIR3DL1/inmunología , Análisis de Secuencia de ADN , Donantes de TejidosRESUMEN
A novel KIR3DL1*0150103 found in West Africa with five single nucleotide polymorphisms compared to KIR3DL1*0150101.
Asunto(s)
Alelos , Polimorfismo de Nucleótido Simple , Receptores KIR3DL1/genética , Donantes de Tejidos , África Occidental , Secuencia de Bases , Trasplante de Médula Ósea , Codón , Exones , Expresión Génica , Humanos , Intrones , Datos de Secuencia Molecular , Tipificación Molecular , Receptores KIR3DL1/inmunología , Alineación de SecuenciaRESUMEN
KIR3DS1*0130109 is similar to KIR3DS1*0130101 except for a A > G change in intron 4.
Asunto(s)
Prueba de Histocompatibilidad , Receptores KIR3DS1/química , Receptores KIR3DS1/genética , Análisis de Secuencia de ADN , Alelos , Secuencia de Bases , Humanos , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Alineación de SecuenciaRESUMEN
An acute injection of estradiol benzoate (EB) to the ovariectomized (OVX) rat activates low levels of lordosis, and subsequent progesterone (P) administration augments lordosis and recruits a complete pattern of sexual behavior including appetitive behaviors (e.g., hops/darts and solicitations). However, repeated injections of 5µg or 10µg EB (but not 2µg EB), administered every 4days to sexually-experienced OVX rats results in a behavioral sensitization, such that lordosis quotients (LQs) and appetitive behaviors progressively increase. We have shown that adrenal P does not play a critical role because behavioral sensitization to EB is not prevented by adrenalectomy. Here we tested whether P receptors play a role by examining the effect of chronic administration of the P receptor antagonist RU486 at a dose that reliably inhibits sexual behavior in fully primed OVX rats. Females were treated with EB (5 or 10µg), and 5mg RU486 dissolved in 0.4mL vehicle (VEH; 80% sesame oil, 15% benzyl benzoate, 5% benzyl alcohol) 48h and 5h prior to each of 7 tests, respectively, occurring at 4-day intervals in unilevel 4-hole pacing chambers. Control animals were treated with 2, 5, or 10µg EB+VEH. As expected, sensitization did not occur in females treated with 2µg EB+VEH, and those females received fewer intromissions and ejaculations than all other groups. RU486 did not prevent the sensitization of LQ, moderate and high lordosis magnitudes (LM2 and LM3) or appetitive sexual behaviors on early tests, and in fact potentiated appetitive behaviors, LQ, LM2 and LM3, consistent with its facilitative actions in females treated with EB-alone, as we and others have reported previously. However, despite the initial facilitation, blocking P receptors by chronic administration of RU486 inhibited the maintenance of behavioral sensitization to EB.
Asunto(s)
Estradiol/análogos & derivados , Mifepristona/farmacología , Conducta Sexual Animal/efectos de los fármacos , Animales , Conducta Apetitiva/efectos de los fármacos , Eyaculación/efectos de los fármacos , Estradiol/farmacología , Femenino , Humanos , Masculino , Ovariectomía , Postura , Progesterona/farmacología , Ratas , Ratas Long-Evans , Receptores de Progesterona/metabolismo , Conducta Sexual Animal/fisiología , Factores de TiempoRESUMEN
Exposure to testosterone during a critical period of prenatal development disrupts the normal display of sexual behaviors in adult ovariectomized (OVX) rats treated with estradiol benzoate (EB) followed by progesterone (P). The organizational hypothesis posits that prenatally androgenized females (PNAFs) are desensitized to EB. We tested this hypothesis by first treating PNAFs with varying doses of EB (2.5, 5, 10, 20µg) followed by P (500µg), and second by subjecting females to an established EB behavioral sensitization paradigm where females are first given sexual experience with EB (10µg) and P prior to repeated sexual behavior testing with EB alone. Long-Evans females were androgenized in utero by a s.c. injection of 500µg testosterone propionate or the oil control to pregnant dams on gestational day 18. Female offspring were OVX on postnatal day 80 and tested one week later in the unilevel 4-hole pacing chamber. Genital tissue was defeminized in PNAFs, and the lordosis quotient (LQ) and partial (i.e., hops/darts) and full solicitations were significantly lower, while defensive behaviors were higher, in PNAF females, relative to non-PNAF females regardless of the acute EB priming dose. However, repeated testing with EB alone (10µg), or EB and P eliminated the differences between groups on LQ and hops/darts, indicating that the behavioral deficit can be overcome by sexual experience. These results suggest that PNAFs are not desensitized to EB, and despite disruptions in sexual differentiation of anatomical structures, the deficiency in sexual behavior in response to acute EB and P can be experientially overcome. PNAFs appear, however, to have a chronic deficit in the expression of full solicitations.
Asunto(s)
Andrógenos/efectos adversos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Conducta Sexual Animal/efectos de los fármacos , Virilismo/inducido químicamente , Andrógenos/administración & dosificación , Animales , Estradiol/administración & dosificación , Estradiol/efectos adversos , Estradiol/análogos & derivados , Femenino , Humanos , Ovariectomía , Postura , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Ratas Long-Evans , Conducta Sexual Animal/fisiología , Maduración Sexual/efectos de los fármacos , Maduración Sexual/fisiología , Virilismo/fisiopatología , Virilismo/psicologíaRESUMEN
Through the successful implementation of policies to prevent mother-to-child-transmission (PMTCT) of HIV-1 infection, children born to HIV-1-infected mothers are now much less likely to acquire HIV-1 infection than previously. Nevertheless, HIV-1-exposed uninfected (HEU) children have substantially increased morbidity and mortality compared with children born to uninfected mothers (unexposed uninfected, UU), predominantly from infectious causes. Moreover, a range of phenotypical and functional immunological differences between HEU and UU children has been reported. As the number of HEU children continues to increase worldwide, two questions with clear public health importance need to be addressed: first, does exposure to HIV-1 and/or ARTâ in utero or during infancy have direct immunological consequences, or are these poor outcomes simply attributable to the obvious disadvantages of being born into an HIV-affected household? Secondly, can we expect improved maternal care and ART regimens during and after pregnancy, together with optimized infant immunization schedules, to reduce the excess morbidity and mortality of HEU children?
Asunto(s)
Infecciones por VIH/inmunología , VIH-1/inmunología , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo/inmunología , Antivirales/inmunología , Antivirales/uso terapéutico , Femenino , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , VIH-1/efectos de los fármacos , Humanos , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/inmunología , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & controlRESUMEN
Full-length sequence of KIR3DL1*0150102 differs from that of KIR3DL1*0150101 in intron 6.
Asunto(s)
Intrones , Receptores KIR3DL1/genética , Secuencia de Bases , Humanos , Datos de Secuencia MolecularRESUMEN
KIR3DL1*0150211 differs from KIR3DL1*0150201 with six single nucleotide polymorphisms in introns 3, 4, 5, and 6.
Asunto(s)
Alelos , Polimorfismo de Nucleótido Simple , Receptores KIR3DL1/genética , Secuencia de Bases , Humanos , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
The full-length genomic sequence of KIR3DL1*0040103 differs from KIR3DL1*0040101 at three nucleotide positions.
Asunto(s)
Alelos , Receptores KIR3DL1/genética , Secuencia de Bases , Población Negra , Humanos , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
The complete length genomic sequence of KIR3DL1*03101 differs from KIR3DL1*0010101 at multiple intronic and exonic sites.