The nucleic acid chaperone activity of the HIV-1 Gag polyprotein is boosted by its cellular partner RPL7: a kinetic study
NUCLEIC ACIDS RESEARCH
Authors: Karnib, Hassan; Nadeem, Muhammad F.; Humbert, Nicolas; Sharma, Kamal K.; Grytsyk, Natalia; Tisne, Carine; Boutant, Emmanuel; Lequeu, Thiebault; Real, Eleonore; Boudier, Christian; de Rocquigny, Hugues; Mely, Yves
Abstract
The HIV-1 Gag protein playing a key role in HIV-1 viral assembly has recently been shown to interact through its nucleocapsid domain with the ribosomal protein L7 (RPL7) that acts as a cellular co-factor promoting Gag's nucleic acid (NA) chaperone activity. To further understand howthe two proteins act together, we examined their mechanism individually and in concert to promote the annealing between dTAR, the DNA version of the viral transactivation element and its complementary cTAR sequence, taken as model HIV-1 sequences. Gag alone or complexed with RPL7 was found to act as a NA chaperone that destabilizes cTAR stem-loop and promotes its annealing with dTAR through the stem ends via a two-step pathway. In contrast, RPL7 alone acts as a NA annealer that through its NA aggregating properties promotes cTAR/dTAR annealing via two parallel pathways. Remarkably, in contrast to the isolated proteins, their complex promoted efficiently the annealing of cTAR with highly stable dTARmutants. This was confirmed by the RPL7-promoted boost of the physiologically relevant Gag-chaperoned annealing of (+)PBS RNA to the highly stable tRNALys 3 primer, favoring the notion that Gag recruits RPL7 to overcome major roadblocks in viral assembly.
Prevalence and epidemiological characteristics of human immunodeficiency virus-1 infection in an iron mining area with intense migratory flow in Para State, Brazilian amazon, 2005-2014
BRAZILIAN JOURNAL OF MICROBIOLOGY
Authors: Macedo, Olinda; Freitas, Felipe Bonfim; dos Reis, Raimundo Macedo; Bensabath, Gilberta; Nunes, Heloisa Marciliano; Siqueira, Jones Anderson Monteiro; Gabbay, Yvone Benchimol
Abstract
Acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) is a major global public health problem. The aim of this study is to determine the prevalence of HIV-1 infection in four municipalities of Para State (Maraba, Parauapebas, Curionopolis, and Canaa dos Carajas), in northern, Brazil. The municipalities are located in the Carajas Complex iron mining area. The employment opportunities result in extensive migratory flow of people. A total of 4771 serum samples were obtained from 2005 to 2014 and were sent to Evandro Chagas Institute, Belem-Para, where they were tested by enzyme-linked immunosorbent assay, with reactive samples confirmed by Western blot analysis. The samples were from individuals from 23 Brazilian states and the Federal District, mainly Maranhao (39.53%) and other municipalities of Para (34.25%). The total positivity rate was 0.48% (23/4771). The rate was 0.47% (14/2975) in males and 0.50% (9/1796) in females. Of these, 0.33% (14/4275) were from asymptomatic individuals whose serum were collected during the serological survey, 1.81% (9/497) were from cases featuring clinical symptoms including fever/diarrhea/jaundice, which were included in febrile, diarrheal, and icteric syndromes analyzed during the study. The findings indicated the presence of HIV-1 infection in the general population studied. The majority of cases (60.9%, 14 of 23 positive cases) were asymptomatic.