RESUMO
The HIV-1 capsid is a fullerene cone made of quasi-equivalent hexamers and pentamers of the viral CA protein. Typically, quasi-equivalent assembly of viral capsid subunits is controlled by a molecular switch. Here, we identify a Thr-Val-Gly-Gly motif that modulates CA hexamer/pentamer switching by folding into a 310 helix in the pentamer and random coil in the hexamer. Manipulating the coil/helix configuration of the motif allowed us to control pentamer and hexamer formation in a predictable manner, thus proving its function as a molecular switch. Importantly, the switch also remodels the common binding site for host factors that are critical for viral replication and the new ultra-potent HIV-1 inhibitor lenacapavir. This study reveals that a critical assembly element also modulates the post-assembly and viral replication functions of the HIV-1 capsid and provides new insights on capsid function and inhibition.
Assuntos
Capsídeo , HIV-1 , Capsídeo/química , HIV-1/química , Proteínas do Capsídeo/químicaRESUMO
Brazilian data for maternal GBS colonization shows different prevalence rates. This conflicting data may be related to the absence of an official recommendation from the Federal Brazilian Health Authorities describing guidelines and protocols to perform GBS screening in pregnant women, in both public and private clinics. In the present review, we evaluated published reports addressing the prevalence of GBS in different regions of the country, methods used, and, when available, information regarding antibiotic resistance and serological typing of clinical isolates. According to this review, GBS prevalence in pregnant women in Brazil ranged from 4.2 to 28.4%, in the last 10 years. Serotype Ia was the most prevalent. The highest antibiotic resistance rates were found for tetarcycline, although its use to treat GBS infections is not common. Our results also show high resistance rates to clindamycin and erythromycin, which are commonly used as an alternative to penicillin in GBS infecctions. The increased antibiotic resistance, variations in serotype distribution, and high GBS prevalences need to be further investigated. Based on the present situation, recommendations regarding GBS surveillance in the country were raised and may improve our strategies for preventing neonatal infections.