Binding kinetics of highly mutated HIV-1 subtype C protease inhibition by Lopinavir and Darunavir in the face of altered conformational dynamics.

Highly mutated HIV-1 protease (PR) compromises the efficacy of lopinavir (LPV) and darunavir (DRV) used to formulate salvage regimens in HIV/AIDS management. Here, we report the kinetics of inhibition of lopinavir (LPV) and darunavir (DRV) on highly mutated South African HIV-1 subtype C PR obtained from clinical isolates. The wild-type and mutant South African HIV-1 subtype C PR were cloned and purified.

The (Re-)Emergence and Spread of Viral Zoonotic Disease: A Perfect Storm of Human Ingenuity and Stupidity.

Diseases that are transmitted from vertebrate animals to humans are referred to as zoonotic diseases. Although microbial agents such as bacteria and parasites are linked to zoonotic events, viruses account for a high percentage of zoonotic diseases that have emerged. Worryingly, the 21st century has seen a drastic increase in the emergence and re-emergence of viral zoonotic disease.

Characterization of a Near Full-Length Hepatitis E Virus Genome of Subtype 3c Generated from Naturally Infected South African Backyard Pigs.

Eight genotypes of the hepatitis E virus (Orthohepevirus A; HEV) designated HEV-1 to HEV-8 have been reported from various mammalian hosts. Notably, domestic pigs and wild boars are the natural reservoirs of HEV-3 and HEV-4 genotypes with zoonotic propensity. Since HEV infection in domestic pigs is usually subclinical, it may remain undetected, facilitating zoonotic spillover of HEV to the exposed human populations.

Metagenomic Analysis of RNA Fraction Reveals the Diversity of Swine Oral Virome on South African Backyard Swine Farms in the uMgungundlovu District of KwaZulu-Natal Province.

Numerous RNA viruses have been reported in backyard swine populations in various countries. In the absence of active disease surveillance, a persistent knowledge gap exists on the diversity of RNA viruses in South African backyard swine populations. This is the first study investigating the diversity of oral RNA virome of the backyard swine in South Africa.

The HIV-1 Gag Protein Displays Extensive Functional and Structural Roles in Virus Replication and Infectivity.

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.

An overview of influenza A virus genes, protein functions, and replication cycle highlighting important updates.

The recent research findings on influenza A virus (IAV) genome biology prompted us to present a comprehensive overview of IAV genes, protein functions, and replication cycle. The eight gene segments of the IAV genome encode 17 proteins, each having unique functions contributing to virus fitness in the host. The polymerase genes are essential determinants of IAV pathogenicity and virulence; however, other viral components also play crucial roles in the IAV replication, transmission, and adaptation.

A systematic review of influenza A virus prevalence and transmission dynamics in backyard swine populations globally.

Background: Backyard swine farming is critical to generating subsistence and food security in rural and peri-urban households in several developing countries. The objective of this systematic review was to analyze the molecular and serological prevalence of influenza A virus (IAV) in backyard swine populations globally.

Results: We identified 34 full-text research articles in NCBI-PubMed and Google Scholar databases that have reported IAV sero- and/or virological prevalence in backyard swine up to 11 July 2021.

Review of genome sequencing technologies in molecular characterization of influenza A viruses in swine.

The rapidly evolving antigenic diversity of influenza A virus (IAV) genomes in swine makes it imperative to detect emerging novel strains and track their circulation. We analyzed in our review the sequencing technologies used for subtyping and characterizing swine IAV genomes. Google Scholar, PubMed, and International Nucleotide Sequence Database Collaboration (INSDC) database searches identified 216 studies that have utilized Sanger, second-, and third-generation sequencing techniques to subtype and characterize swine IAV genomes up to 31 March 2021.

Deciphering transmission dynamics and spillover of avian influenza viruses from avian species to swine populations globally.

Genome sequences of eleven avian influenza virus (AIV) subtypes have been reported in swine populations from seven countries until August 2020. To unravel the transmission dynamics and spillover events of AIVs from avian reservoirs to swine, full-length hemagglutinin (HA) sequences of AIV subtypes (n = 11) reported from various avian species and swine were retrieved from the 'Influenza Research Database'. Phylogenetic analysis identified closely related avian and swine AIV sequences suggesting potential spillover events from multiple domestic and wild avian species, including chicken, duck, pigeon, goose, quail, and aquatic birds to swine.

Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch.

Understanding the underlying molecular interaction during a therapy switch from lopinavir (LPV) to darunavir (DRV) is essential to achieve long-term virological suppression. We investigated the kinetic and structural characteristics of multidrug-resistant South African HIV-1 subtype C protease (HIV-1 PR) during therapy switch from LPV to DRV using enzyme activity and inhibition assay, fluorescence spectroscopy, and molecular dynamic simulation. The HIV-1 protease variants were from clinical isolates with a combination of drug resistance mutations; MUT-1 (M46I, I54V, V82A, and L10F), MUT-2 (M46I, I54V, L76V, V82A, L10F, and L33F), and MUT-3 (M46I, I54V, L76V, V82A, L90M, and F53L).

Recombinant expression of HIV-1 protease using soluble fusion tags in Escherichia coli: A vital tool for functional characterization of HIV-1 protease.

HIV-1 protease expression in the laboratory is demanding because of its high cytotoxicity, making it difficult to express in bacterial expression systems such as Escherichia coli. To overcome these challenges, HIV-1 protease fusion with solubility enhancing tags helps to mitigate its cytotoxic effect and drive its expression as a soluble protein. Therefore, this review focuses on the expression of bioactive HIV-1 protease using solubility-enhancing fusion tags in Escherichia coli and summarises the characteristic features of the different common fusion tags that have been used in the expression of HIV-1 protease.

A Systematic Review Analyzing the Prevalence and Circulation of Influenza Viruses in Swine Population Worldwide.

The global anxiety and a significant threat to public health due to the current COVID-19 pandemic reiterate the need for active surveillance for the zoonotic virus diseases of pandemic potential. Influenza virus due to its wide host range and zoonotic potential poses such a significant threat to public health. Swine serve as a "mixing vessel" for influenza virus reassortment and evolution which as a result may facilitate the emergence of new strains or subtypes of zoonotic potential.

Tuberculous meningitis is associated with higher cerebrospinal HIV-1 viral loads compared to other HIV-1-associated meningitides.

To gain a better understanding of the immunopathogenesis of tuberculous meningitis (TBM) and identify potential diagnostic biomarkers that may discriminate TBM from other HIV-1-associated meningitides, we assessed HIV-1 viral load levels, drug resistance patterns in antiretroviral therapy (ART)-experienced patients with persistent viremia and soluble immunological analytes in peripheral blood and cerebrospinal fluid (CSF) of HIV-1 infected patients with TBM versus other meningitides. One hundred and three matched blood and CSF samples collected from HIV-1 infected patients with TBM or other meningitides presenting at a hospital in Durban, South Africa, from January 2009 to December 2011 were studied. HIV-1 RNA and 28 soluble immunological potential biomarkers were quantified in blood plasma and CSF.

Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals.

The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals.

Characterization of anti-HIV-1 neutralizing and binding antibodies in chronic HIV-1 subtype C infection.

Neutralizing (nAbs) and high affinity binding antibodies may be critical for an efficacious HIV-1 vaccine. We characterized virus-specific nAbs and binding antibody responses over 21 months in eight HIV-1 subtype C chronically infected individuals with heterogeneous rates of disease progression. Autologous nAb titers of study exit plasma against study entry viruses were significantly higher than contemporaneous responses at study entry (p=0.

Drug resistance and coreceptor usage in HIV type 1 subtype C-infected children initiating or failing highly active antiretroviral therapy in South Africa.

HIV-1 drug resistance monitoring in resource-poor settings is crucial due to limited drug alternatives. Recent reports of the increased prevalence of CXCR4 usage in subtype C infections may have implications for CCR5 antagonists in therapy. We investigated the prevalence of drug resistance mutations and CXCR4 coreceptor utilization of viruses from HIV-1 subtype C-infected children.

Drug resistance pattern of HIV type 1 isolates sampled in 2007 from therapy-naive pregnant women in North-Central Nigeria.

In Nigeria, the country with the second largest number of HIV-1-infected people globally, antiretroviral therapy rollout is now widespread with an increasing number of individuals and communities benefitting. However, the drug resistance profile of patients initiating or failing on antiretroviral therapy is not well characterized. Here we studied the molecular variability of the protease and reverse transcriptase region of isolates from therapy-naive pregnant women in North-Central Nigeria (one of the geopolitical zones with the highest prevalence of HIV in Nigeria) to identify baseline mutations with potential drug resistance implications.

Genetic characteristics, coreceptor usage potential and evolution of Nigerian HIV-1 subtype G and CRF02_AG isolates.

HIV-1 CRF02_AG and subtype G (HIV-1G) account for most HIV infections in Nigeria, but their evolutionary trends have not been well documented. To better elucidate the dynamics of the epidemic in Nigeria we characterised the gag and env genes of North-Central Nigerian HIV-1 isolates from pregnant women. Of 28 samples sequenced in both genes, the predominant clades were CRF02_AG (39%) and HIV-1G (32%).

HIV-1 subtype C envelope characteristics associated with divergent rates of chronic disease progression.

Background: HIV-1 envelope diversity remains a significant challenge for the development of an efficacious vaccine. The evolutionary forces that shape the diversity of envelope are incompletely understood. HIV-1 subtype C envelope in particular shows significant differences and unique characteristics compared to its subtype B counterpart.

Development of dual-class antiretroviral drug resistance in a child coinfected with HIV and tuberculosis: a case report from KwaZulu-Natal, South Africa.

The treatment of concurrent HIV and tuberculosis (TB) in children <3 years of age has not been well-studied and is complicated by potential drug-drug interactions. The recommended antiretroviral therapy (ART) in coinfected children in South Africa consists of full-strength ritonavir, lamivudine and stavudine. We report on a child initiated on this regimen, during concurrent TB treatment, who promptly developed an adverse reaction, virologic failure and dual-class antiretroviral drug resistance, compromising subsequent salvage ART.