RESUMEN
HIV-1 coreceptors CCR5 and CXCR4 play an important role in viral entry and pathogenesis. To better understand the role of viral tropism in HIV-1 transmission, we examined the coreceptor utilization of viral isolates obtained from men enrolled in a study of heterosexual transmission in northern Thailand. Viral isolates were obtained from HIV-1-positive males who had either HIV-1-infected spouses (RM; n = 5) or HIV-1-uninfected spouses (HM; n = 10). Viral isolates from 1 of the 5 RM males and 2 of the 10 HM males were CCR5 tropic, whereas isolates from 3 RM males and 6 of the HM male isolates were CXCR4 tropic. Of the nine X4-tropic isolates, seven also used at least one of the following coreceptors: CCR8, CCR1, CCR2b, or CX3CR1, and none employed CCR5 as an additional coreceptor. More importantly, three isolates, RM-15, HM-13, and HM-16 (one from a transmitter and two from nontransmitter), did not infect GHOST4.cl.34 cells expressing any of the known coreceptors. Further analysis using MAGI-plaque assays, which allow visualization of infected cells, revealed that RM-15 had low numbers of infected cells in MAGI-R5 and MAGI-X4 cultures, whereas HM-13 and HM-16 had high levels of plaques in MAGI-X4 cultures. Replication kinetics using activated lymphocytes revealed that these three isolates replicated in CCR5(+/+) as well as CCR5(-/-) peripheral blood mononuclear cells, suggesting that these isolates did not have an absolute requirement of CCR5 for viral entry. All three isolates were sensitive to the X4-antagonistic compounds T-22 and AMD3100. Analysis of the C2V3 region did not reveal any significant structural differences between any of the Thai subtype E isolates. Thus, there was no association between the pattern of coreceptor usage and transmissibility among these subtype E HIV-1 isolates.
Asunto(s)
Infecciones por VIH/virología , VIH-1/metabolismo , Receptores del VIH/metabolismo , Secuencia de Aminoácidos , Receptor 1 de Quimiocinas CX3C , Quimiocina CCL2/metabolismo , Quimiocinas CC/metabolismo , Secuencia de Consenso , Transmisión de Enfermedad Infecciosa , Proteína gp120 de Envoltorio del VIH/química , Infecciones por VIH/transmisión , VIH-1/clasificación , VIH-1/patogenicidad , Heterosexualidad , Humanos , Masculino , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Receptores CCR1 , Receptores CCR2 , Receptores CCR5/metabolismo , Receptores CCR8 , Receptores CXCR4/metabolismo , Receptores de Quimiocina/metabolismo , Receptores de Citocinas/metabolismo , Receptores del VIH/química , Tailandia , Replicación ViralRESUMEN
BACKGROUND: Thailand's epidemic of HIV infection, which began in 1988, has primarily involved heterosexual transmission of the virus. This study describes changes in prevalence of HIV and other infectious diseases among blood donors in northern Thailand from 1990 through 2001. STUDY DESIGN AND METHODS: Serologic screening results and demographic data were analyzed from 276,066 donors screened at two blood collection facilities in Chiang Mai, Thailand, from 1990 through 2001. RESULTS: The HIV prevalence peaked in 1991 to 1993 at 4.04 percent and then declined to 0.38 percent in 2001. The overall prevalence of HIV infection was 2.16 percent; HIV prevalence was higher among male (2.24%) than among female (0.64%) donors, in first-time donors, and in replacement volunteer donors. The majority of the donors were men and first-time donors throughout this study. The prevalence of antibodies to syphilis decreased significantly in both men and women. However, the prevalence of antibodies to HCV and HBsAg were stable. CONCLUSIONS: The declining HIV prevalence from 1990 through 2001 among blood donors in two large blood banks in northern Thailand indicates significant progress toward recruitment of a safer donor population in a developing country despite a major HIV and AIDS epidemic involving the general population.