Release of Infectious Hepatitis C Virus from Huh7 Cells Occurs via a trans-Golgi Network-to-Endosome Pathway Independent of Very-Low-Density Lipoprotein Secretion

The release of infectious hepatitis C virus (HCV) particles from infected cells remains poorly characterized. We previously demonstrated that virus release is dependent on the endosomal sorting complex required for transport (ESCRT). Here, we show a critical role of trans-Golgi network (TGN)-endosome trafficking during the assembly, but principally the secretion, of infectious virus. This was demonstrated by both small interfering RNA (siRNA)-mediated silencing of TGN-associated adaptor proteins and a panel of dominant negative (DN) Rab GTPases involved in TGN-endosome trafficking steps. Importantly, interfering with factors critical for HCV release did not have a concomitant effect on secretion of triglycerides, ApoB, or ApoE, indicating that particles are likely released from Huh7 cells via pathways distinct from that of very-low-density lipoprotein (VLDL). Finally, we show that HCV NS2 perturbs TGN architecture, redistributing TGN membranes to closely associate with HCV core protein residing on lipid droplets. These findings support the notion that HCV hijacks TGN-endosome trafficking to facilitate particle assembly and release. Moreover, although essential for assembly and infectivity, the trafficking of mature virions is seemingly independent of host lipoproteins

Beneficência e paternalismo médico Beneficence and medical paternalism

O autor discute a relação médico-paciente, considerando que na sociedade contemporânea e secularizada as aplicações decorrentes das pesquisas biomédicas trazem dilemas ao exercício profissional. Discorre sobre o atendimento, analisando o paternalismo e a autonomia do paciente na perspectiva dos princípios da beneficência e da autonomia. A beneficência se constitui em uma das prerrogativas do exercício da Medicina dizendo respeito a agir no melhor interesse do paciente. Para a reflexão bioética sua aplicação importa em distinguir a beneficência geral da específica quando da tomada de decisão médica. Desconsiderar a opinião do paciente plenamente capaz constitui conduta unilateral, o paternalismo médico, que pode ser eticamente justificado, e por vezes necessário, apenas quando existe limitação na autodeterminação do paciente, momentânea ou definitiva. Torna-se necessário, portanto, entender que as ações beneficentes no atendimento clínico são inerentes à relação médico-paciente e quanto melhor essa relação é construída, tanto melhor será a decisão médica, que não cause dano ao paciente e possa agir em seu benefício, respeitando sua autonomia. Para compatibilizar beneficência e paternalismo o médico precisa manter sua autoridade, preservando seus conhecimentos e responsabilizando-se pela tomada da decisão, e o paciente participar do processo de escolha de acordo com seus valores morais e pessoais.<br>The author addresses the relevant issue of the relationship between doctor and patient, considering that biomedical research applications could raise dilemmas to the medical profession's practice in a contemporary and secular society. In this context, he seeks to discuss the medical attendance and analyses aspects concerned with paternalism and the prerogatives of patient's autonomy in perspective of the beneficence and autonomy principles. The beneficence constitutes one of the prerogatives in Medicine practice and relates to acting in the patient's best interest; beneficence takes on a character of bioethics reflection, and the application of the rules implies distinguishing general beneficence from specific beneficence; making medical decision without considering the opinion from a fully capable patient constitutes an unilateral conduct, called medical paternalism; paternalism can be ethically justified, and sometimes necessary, when there is a temporary or permanent limitation of the patient's self-determination; it is necessary to understand that the application of beneficence actions on a medical attendance takes place within a doctor/patient relationship. The better this relationship is built up, the better the doctor's decision will be in not causing damage to the patient until the procedures of acting for his benefit, respecting his autonomy. We believe that beneficence and paternalism would be more compatible in a relationship where the doctor kept his authority, preserving his knowledge and taking responsibility for making decision, and the patient, in turn, would also take part according to his moral and personal values