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Due to high human immunodeficiency virus type 1 (HIV-1) subtype C infections coupled with increasing antiretroviral treatment failure, the elucidation of complex drug resistance mutational patterns arising through protein co-evolution is required. Despite the inclusion of potent protease inhibitors Lopinavir (LPV) and Darunavir (DRV) in second- and third-line therapies, many patients still fail treatment due to the accumulation of mutations in protease (PR) and recently, Gag. To understand the co-evolutionary molecular mechanisms of resistance in the HIV-1 PR and Gag, we performed 100 ns molecular dynamic simulations on multidrug resistant PR’s when bound to LPV, DRV or a mutated A431V NC|p1 Gag cleavage site (CS). Here we showed that distinct changes in PR’s active site, flap and elbow regions due to several PR resistance mutations (L10F, M46I, I54V, L76V, V82A) were found to alter LPV and DRV drug binding. However, binding was significantly exacerbated when the mutant PRs were bound to the NC|p1 Gag CS. Although A431V was shown to coordinate several residues in PR, the L76V PR mutation was found to have a significant role in substrate recognition. Consequently, a greater binding affinity was observed when the mutated substrate was bound to an L76V-inclusive PR mutant (Gbind: −62.46 ± 5.75 kcal/mol) than without (Gbind: −50.34 ± 6.28 kcal/mol). These data showed that the co-selection of resistance mutations in the enzyme and substrate can simultaneously constrict regions in PR’s active site whilst flexing the flaps to allow flexible movement of the substrate and multiple, complex mechanisms of resistance to occur. Communicated by Ramaswamy H. Sarma

Once merely thought of as the protein responsible for the overall physical nature of the human immunodeficiency virus type 1 (HIV-1), the Gag polyprotein has since been elucidated to have several roles in viral replication and functionality. Over the years, extensive research into the polyproteins’ structure has revealed that Gag can mediate its own trafficking to the plasma membrane, it can interact with several host factors and can even aid in viral genome packaging. Not surprisingly, Gag has also been associated with HIV-1 drug resistance and even treatment failure. Therefore, this review provides an extensive overview of the structural and functional roles of the HIV-1 Gag domains in virion integrity, functionality and infectivity.

The use of rivers for recreational and domestic practices makes it imperative to scrutinize the water quality circulating within surrounding communities. The complexity of biological, physical and chemical constituents in water is constantly evolving. This study evaluated various microbial and physico-chemical parameters in a polluted river system over a 12-month period. Apart from an increase in chemical pollutants, elevated levels of E. coli, total (TC) and faecal (FC) coliforms, and Shigella species could be attributed to faecal contamination entering the catchment. Canonical correspondence analysis revealed a strong relationship between FC, TC and temperature whereas moderate interactions was seen between total dissolved solids, electrical conductivity, TC and FC populations. Furthermore, close relationships between the bacterial and phage communities were also observed. The complex interactions of these physico-chemical and microbial indicators could be due to anthropogenic activities, changing climatic conditions and the excreta of infected and non-infected individuals entering the river. Assessing the complexity of aquatic ecosystems can aid in the development of novel, customizable, inexpensive water purification tools.

Due to the continued persistence of waterborne viral-associated infections, the presence of enteric viruses is a concern. Notwithstanding the health implications, viral diversity and abundance is an indicator of water quality declination in the environment. The aim of this study was to evaluate the presence of viruses (bacteriophage and enteric viruses) in a highly polluted, anthropogenic-influenced river system over a 6-month period at five sampling points. Cytopathic-based tissue culture assays revealed that the isolated viruses were infectious when tested on Hep-G2, HEK293 and Vero cells. While transmission electron microscopy (TEM) revealed that the majority of the viruses were bacteriophages, a number of presumptive enteric virus families were visualized, some of which include Picornaviridae, Adenoviridae, Polyomaviridae and Reoviridae. Finally, primer specific nested polymerase chain reaction (nested-PCR)/reverse transcription-polymerase chain reaction (RT-PCR) coupled with BLAST analysis identified human adenovirus, polyomavirus and hepatitis A and C virus genomes in river water samples. Taken together, the complexity of both bacteriophage and enteric virus populations in the river has potential health implications. Finally, a systematic integrated risk assessment and management plan to identify and minimize sources of faecal contamination is the most effective way of ensuring water safety and should be established in all future guidelines.

The ecological role of viruses in aquatic environments is gaining interest due to their abundance and overall diversity. Much focus has been on bacteriophages since they were found to play an important role in the diversification and sustainment at both the micro- and macro-scale. However, the discovery of virophages coexisting with giant viruses in a diverse set of eukaryotic hosts has recently gained attention. Virophages are small double-stranded DNA viruses found parasitizing giant viruses of eukaryotes. Since the discovery of the first virophage (Sputnik) many virophage signatures have been detected from a variety of environmental samples with specific infection cycles. In addition, these parasites display important roles in equilibrating microbial biomass, nutrient cycling and population dynamics. Moreover, virophage-induced evolution between giant viruses and their hosts have also been described. Considering the ongoing discovery of virophages and their dynamics in aquatic ecosystems, this review intends to provide an update of the virophage signatures identified to date, also tending to provide insight on the mechanisms of coinfection as well as their role as agents of biodiversity and nutrient cyclers in water environments.