Update on HIV-1 diversity in Africa: a decade in review.

Background: HIV-1 strains have diversified extensively through mutation and recombination since their initial transmission to human beings many decades ago in Central Africa in the first part of the 20th Century (between 1915 and 1941). The upward trend in global HIV-1 diversity has continued unabated, with newer groups, subtypes, and unique and circulating recombinants increasingly being reported, especially in Africa.

Objective: In this review, we focus on the extensive diversity of HIV-1 over a decade (2000-2011), in 51 countries of the three African geographic regions (eastern and southern, western and central, and northern Africa) as per the WHO/UNAIDS 2010 classification.

Viruses and host evolution: virus-mediated self identity.

Virus evolution has become a topic that involves population based selection. Both quasispecies based populations and reticulated mosaic exchange of populations of genetic elements are now well established. This has led us to the understanding that a cooperative consortia can be a crucial aspect of virus driven evolution.

Viral ancestors of antiviral systems.

All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA.

Evidence of the circulation of pandemic influenza (H1N1) 2009 with D222D/G/N/S hemagglutinin polymorphisms during the first wave of the 2009 influenza pandemic.

Background: The hemagglutinin HA1 D222G substitution may be associated with adverse outcomes in pandemic influenza A (H1N1) 2009 infections by enhancing the binding capacity of α2-3 sialyl receptors to pandemic influenza (H1N1) 2009 viruses.

Objectives: To investigate the emergence of the D222G mutation and other polymorphisms at this position during the first southern hemisphere pandemic wave in 2009.

Study Design: A total of 127 samples that were nucleic acid test positive for pandemic influenza (H1N1) 2009 virus were subjected to a sequence-based genotypic assessment of viral populations.

HIV type 1 subtype surveillance in central Kenya.

Human immunodeficiency virus 1 (HIV-1) infection is characterized by genetic diversity such that specific viral subtypes are predominant in specific geographic areas. To determine circulating subtypes of HIV-1 in different parts of central Kenya, a cross-sectional study was carried out on HIV-1-positive blood samples collected from consenting individuals in eight hospitals of Kenya's central province. Proviral DNA was extracted from peripheral blood mononuclear cells.

An XMRV derived retroviral vector as a tool for gene transfer.

Background: Retroviral vectors are widely used tools for gene delivery and gene therapy. They are useful for gene expression studies and genetic manipulation in vitro and in vivo. Many retroviral vectors are derived from the mouse gammaretrovirus, murine leukemia virus (MLV).

Genome-wide analysis of primary CD4+ and CD8+ T cell transcriptomes shows evidence for a network of enriched pathways associated with HIV disease.

Background: HIV preferentially infects CD4+ T cells, and the functional impairment and numerical decline of CD4+ and CD8+ T cells characterize HIV disease. The numerical decline of CD4+ and CD8+ T cells affects the optimal ratio between the two cell types necessary for immune regulation. Therefore, this work aimed to define the genomic basis of HIV interactions with the cellular transcriptome of both CD4+ and CD8+ T cells.

Genetic characterization of HIV type 1 among patients with suspected immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy in Kenya.

Antiretroviral therapy (ART) has improved the survival of HIV patients but is also associated with unique manifestations of disease in some subjects during the initial months of therapy. Immune reconstitution inflammatory syndrome (IRIS) is a disorder among individuals starting ART, with no evidence-based treatment and management guidelines. We characterized HIV-1 and determined drug resistance among 14 Kenyan patients with suspected IRIS after ART initiation in 2005.

First evidence of overlaps between HIV-Associated Dementia (HAD) and non-viral neurodegenerative diseases: proteomic analysis of the frontal cortex from HIV+ patients with and without dementia.

Background: The pathogenesis of HIV-associated dementia (HAD) is poorly understood. To date, detailed proteomic fingerprinting directly from autopsied brain tissues of HAD and HIV non-dementia patients has not been performed.

Result: Here, we have analyzed total proteins from the frontal cortex of 9 HAD and 5 HIV non-dementia patients.

Detection of the rapid emergence of the H275Y mutation associated with oseltamivir resistance in severe pandemic influenza virus A/H1N1 09 infections.

In 2009 a new swine-origin influenza virus A/H1N1 (A/H1N1 09) emerged, causing the century's first pandemic. Most isolates of the new A/H1N1 09 virus are susceptible to neuraminidase inhibitors, but the H275Y mutation in the neuraminidase gene region associated with high-level oseltamivir resistance has been detected. Using rolling circle amplification (RCA) technology, 96 A/H1N1 09-specific RT-PCR positive clinical samples collected from 80 oseltamivir-treated and untreated patients were screened for the presence of the H275Y mutation.

HIV reservoirs in vivo and new strategies for possible eradication of HIV from the reservoir sites.

Even though the treatment of human immunodeficiency virus (HIV)-infected individuals with highly active antiretroviral therapy (HAART) provides a complete control of plasma viremia to below detectable levels (<40 copies/mL plasma), there is an unequal distribution of all antiretroviral drugs across diverse cellular and anatomic compartments in vivo. The main consequence of this is the acquisition of resistance by HIV to all known classes of currently prescribed antiretroviral drugs and the establishment of HIV reservoirs in vivo. HIV has a distinct advantage of surviving in the host via both pre-and postintegration latency.

HIV type 1 subtype diversity and drug resistance among HIV type 1-infected Kenyan patients initiating antiretroviral therapy.

The treatment of HIV-1 infection with antiretroviral drugs has greatly improved the survival of those who are infected. However, HIV-1 diversity and drug resistance are major challenges in patient management, especially in resource-poor countries. To evaluate HIV-1 genetic diversity and drug resistance-associated mutations among drug-naive patients in Kenya prior to antiretroviral therapy (ART), a genetic analysis of HIV-1 pol-RT and env-gp41 was performed on samples collected from 53 (18 males and 35 females) consenting patients between April and June 2005.

Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia.

Background: HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.

Methods: To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia.

The source of self: genetic parasites and the origin of adaptive immunity.

Stable colonization of the host by viruses (genetic parasites) can alter the systems of host identity and provide immunity against related viruses. To attain the needed stability, some viruses of prokaryotes (P1 phage) use a strategy called an addiction module. The linked protective and destructive gene functions of an addiction module insures both virus persistence but will also destroy cells that interrupt this module and thereby prevent infection by competitors.

Evaluation of twenty rapid antigen tests for the detection of human influenza A H5N1, H3N2, H1N1, and B viruses.

Twenty rapid antigen assays were compared for their ability to detect influenza using dilutions of virus culture supernatants from human isolates of influenza A H5N1 (clade 1 and 2 strains), H3N2 and H1N1 viruses, and influenza B. There was variation amongst the rapid antigen assays in their ability to detect different influenza viruses. Six of the 12 assays labeled as distinguishing between influenza A and B had comparable analytical sensitivities for detecting both influenza A H5N1 strains, although their ability to detect influenza A H3N2 and H1N1 strains varied.

Persistence pays: how viruses promote host group survival.

Recently, we have realized that viruses numerically dominate all life. Although viruses are known to affect host survival in populations, this has not been previously evaluated in the context of host group selection. Group selection per se is not a currently accepted idea and its apparent occurrence is explained by statistical gene frequency models of kin selection.

Identification of a novel herpes simplex virus type 1 transcript and protein (AL3) expressed during latency.

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected sensory neurons. In small animal models of infection, expression of the first 1.5 kb of LAT coding sequences is necessary and sufficient for wild-type reactivation from latency.

Sensitive detection of the K103N non-nucleoside reverse transcriptase inhibitor resistance mutation in treatment-naïve HIV-1 infected individuals by rolling circle amplification.

Primary or transmitted antiretroviral drug resistance mutations pose a significant obstacle for optimizing antiviral treatment. When present at low-levels, resistance mutations are less likely to be detected by standard genotyping assays. This study utilizes a novel rolling circle amplification (RCA) method using padlock probes to achieve the sensitive, specific and low-level detection of the NNRTI resistance K103N from 59 HIV+ treatment-naïve patients from Beijing, China.

The changing trend of HIV type 1 subtypes in Nairobi.

Monitoring the distribution of HIV-1 subtypes and recombinants among infected individuals has become a priority in HIV therapy. A laboratory analysis of samples collected from HIV-positive patients attending an STI clinic in Nairobi was done between March and May 2004. PCR was carried out on pol (intergrase) and env (C2V3) regions and resulting data on the 54 samples successfully analyzed revealed the following as circulating subtypes: 35/54(65%) were A1/A1, 5/54(9%) were A/C, 4/54 (7%) were A1/D, 1/54 (2%) was C/D, 1/54 (2%) was D/D, 1/54 (2%) was A1/A2, 1/54 (2%)was G/G, 1/54 (2%) was A2/D, 1/54 (2%) was C/C, and 4/54 (7%) were CRF02_ AG.

A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge.

The next generation of needle-free mucosal vaccines is being rationally designed according to rules that govern the way in which the epitopes are recognized by and stimulate the genital mucosal immune system. We hypothesized that synthetic peptide epitopes extended with an agonist of Toll-like receptor 2 (TLR-2), that are abundantly expressed by dendritic and epithelial cells of the vaginal mucosa, would lead to induction of protective immunity against genital herpes. To test this hypothesis, we intravaginally (IVAG) immunized wild-type B6, TLR-2 (TLR2(-/-)) or myeloid differentiation factor 88 deficient (MyD88(-/-)) mice with a herpes simplex virus type 2 (HSV-2) CD8+ T-cell peptide epitope extended by a palmitic acid moiety (a TLR-2 agonist).

Transcriptional profiles in CD8+ T cells from HIV+ progressors on HAART are characterized by coordinated up-regulation of oxidative phosphorylation enzymes and interferon responses.

The functional impairment and numerical decline of CD8+ T cells during HIV infection has a profound effect on disease progression, but only limited microarray studies have used CD8+ T cells. To understand the interactions of HIV and host CD8+ T cells at different disease status, we used the Illumina Human-6 BeadChips to evaluate the transcriptional profile (>48,000 transcripts) in primary CD8+ T cells from HIV+ therapy-naive non-progressors and therapy-experienced progressors. 68 differentially expressed genes were identified, of which 6 have been reported in HIV context, while others are associated with biological functions relevant to HIV pathogenesis.

Short communication: absence of HIV infection in the choroid plexus of two patients who died rapidly with HIV-associated dementia.

Absence of HIV infection of the choroid plexus (CPx) and macrophages in choroidal stroma was observed in two HIV-infected individuals who died 7 weeks and 12 months following the onset of HIV encephalitis. In contrast, the profound macrophage-related pathology associated with HIV infection presented in other neural tissue from 48 brain regions (seven CPx) was analyzed. These data suggest that HIV entry to the CNS may be independent of the CPx.

The possible contribution of HIV-1-induced syncytia to the generation of intersubtype recombinants in vitro.

Objective: To develop a method for single syncytia isolation and delineate the possible contribution of syncytia to intersubtype recombination.

Design: We dually infected whole peripheral mononuclear blood cells with subtype A and D viruses and studied syncytia in vitro and developed a method to isolate individual syncytia to further study HIV variants/dual infections, viral isolation, proviral copies in single syncytia and possible intersubtype recombination in dual cultures containing syncytia using real time PCR.

Methods: Cell culture-based single syncytia isolation, PCR and cloning to determine the nature of HIV variants and real-time PCR to determine proviral copies per individual syncytium and intersubtype recombination in dual cultures.

Rapid identification of infants for antiretroviral therapy in a resource poor setting: the Kenya experience.

In Kenya, HIV diagnosis is not routinely carried out in infants, and yet rapid diagnosis could improve access to lifesaving interventions. A cheap and readily accessible service can resolve this problem, if feasible. In this pilot study the feasibility and costs of provision of an infant HIV diagnosis service in Kenya are evaluated.