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.
Upon entry into a new host cell, the HIV-1 capsid performs multiple essential functions, which include shielding the genome from innate immune sensors, promoting reverse transcription and transporting the core from the entry site at the plasma membrane to the integration site inside the nucleus. The HIV-1 capsid is a fullerene cone made of hexamers and pentamers of the viral CA protein. The two types of capsomers are quasi-equivalent, with the same structural elements mediating distinct inter-subunit contacts. In other studied quasi-equivalent viruses, the capacity of genetically identical subunits to form hexamers and pentamers is conferred by molecular switches. Such a switch has not been previously found in retroviral CA proteins. Here, we report cryoEM structures of the HIV-1 CA pentamer within assembled in vitro capsids at nominal resolutions of 2.4-3.4 Å. Comparison with the hexamer identified an internal loop that adopts distinct conformations, 310 helix in the pentamer and random coil in the hexamer. Designed manipulations of the coil/helix configuration allowed us to control pentamer and hexamer formation in a predictable manner, thus proving its function as a molecular switch. Importantly, the switch controls not only fullerene cone assembly, but also the capsid's capacity to bind post-entry host factors that are critical for viral replication. Furthermore, the switch forms part of the binding site of the new ultra-potent HIV-1 inhibitor, lenacapavir. These studies reveal that a critical assembly element also controls the post-assembly functions of the capsid, and provide new insights on capsid inhibition and uncoating.
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.
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