Angsana Phuphuakrat

Double-Stranded RNA Adenosine Deaminases Enhance Expression of Human Immunodeficiency Virus Type 1 Proteins

ABSTRACT ADARs (adenosine deaminases that act on double-stranded RNA) are RNA editing enzymes that catalyze a change from adenosine to inosine, which is then recognized as guanosine by translational machinery. We demonstrate here that overexpression of ADARs but not of an ADAR mutant lacking editing activity could upregulate human immunodeficiency virus type 1 (HIV-1) structural protein expression and viral production. Knockdown of ADAR1 by RNA silencing inhibited HIV-1 production. Viral RNA harvested from transfected ADAR1-knocked-down cells showed a decrease in the level of unspliced RNA transcripts. Overexpression of ADAR1 induced editing at a specific site in the env gene, and a mutant with the edited sequence was expressed more efficiently than the wild-type viral genome. These data suggested the role of ADAR in modulation of HIV-1 replication. Our data demonstrate a novel mechanism in which HIV-1 employs host RNA modification machinery for posttranscriptional regulation of viral protein expression.

Heterogeneity of HIV-1 Rev response element.

We compiled all the RRE sequences of HIV-1 in the HIV Sequence Database and analyzed for base variation frequency at each nucleotide position. Positions with high frequency of base alteration scattered throughout the region, but primary sequences of almost all bases in stem IIA, Rev-binding bubble, and most of the stem region of stem-loop III were highly conserved. Comparing to HXB2 secondary structure, basepair-disrupting mutations did not distribute evenly in every region of the RRE. Stem I, stem IIB outside the Rev-binding site, stem IIC, and proximal parts of stem IV and V were more variable, while stem IIA, stem III, and distal parts of stem IV and V were highly conserved. These data indicated that RREs are structurally heterogeneous. The uneven distribution of variation in both primary sequence and the stem structure put forward highly conserved sites that might be more crucial to the function of RRE than the less conserved parts.

Functional Variability of Rev Response Element in HIV-1 Primary Isolates

We have previously studied sequence heterogeneity of HIV-1 Rev response element (RRE), and showed uneven variations in different stem–loops of both primary sequence and secondary structure. Here we studied the functional variation of RRE clones from a set of 10 primary isolates, and demonstrated a variation in the function of these RRE clones on the expression of Gag proteins from a truncated HIV-1 genome. The difference in Gag level was, in part, if not exclusively, resulted from the differential efficiency of RNA transport and enhancing of translation. These data suggested that variation of HIV-1 RRE may play a role in regulation of viral replication rate in HIV-1 primary isolates.

Current status of HIV treatment in Asia and the Pacific region

Asia and the Pacific represent a diverse group of nations facing HIV epidemic profiles of differing severity. Compared to other parts of the world, the burden of HIV disease is high in this region because of its large populations. At the end of 2011, 5million people were living with HIV in Asia and the Pacific. This accounted for 15% of people living with HIV worldwide. The prevalence of people living with HIV, as well as access to HIV treatment and care, varies widely between countries. Differences between high-income economies and the rest of the continent are remarkable. Many high-income countries provide antiretroviral therapy (ART) to their citizens. Middle- and low-income countries have rapid ART scale-up and are dependent on international funding. This may compromise the sustainability of ART availability. In addition, lack of access to second- and third-line therapy remains a problem in many countries. The global goal of achieving universal access to ART by 2015 requires mainly low- and middle-income countries to be targeted. Regional policy should be developed in order to identify new infections in key populations, to start earlier treatment, to retain patients in care and to maintain funding.

Coreceptor tropism determined by genotypic assay in HIV-1 circulating in Thailand, where CRF01_AE predominates†

Chemokine (C‐C motif) receptor 5 (CCR5) inhibitors are a novel class of antiretroviral agents that are promising for treatment of patients who harbour the HIV‐1 R5 strain. Data on coreceptor tropism in non‐B HIV‐1 subtypes are limited. We studied coreceptor tropism in HIV‐1 circulating in Thailand, where CRF01_AE predominates, using a genotypic assay.

Selective IgM deficiency in an adult presenting with Streptococcus pneumoniae septic arthritis

Septic arthritis caused by Streptococcus pneumoniae is uncommon. Most of the patients who have invasive pneumococcal infection have underlying diseases associated with impaired immune function. We report a case of polyarticular pneumococcal septic arthritis in a previously healthy adult as the first manifestation of selective immunoglobulin (Ig)M deficiency. The patient had no evidence of autoimmune disease or malignancy. Serum IgG, IgA, and complement levels were normal. Numbers of lymphocyte subsets were in normal range except that of CD4+ cells, which was slightly low. Invasive pneumococcal disease in a healthy adult should lead to further investigation for underlying diseases including primary immunodeficiencies.

Prevalence of HIV infection, access to HIV care, and response to antiretroviral therapy among partners of HIV-infected individuals in Thailand

Background Health care providers usually focus on index HIV-infected patients and seldom obtain information from their partners. We aimed to determine HIV-preventative measures among couples, the prevalence of HIV infection, and treatment outcomes of partners. Methods This cross-sectional study was conducted in two hospital settings, a university hospital in Bangkok and a general hospital in northeastern Thailand, from January 2011-October 2015. Factors associated with serodiscordant relationships were determined by logistic regression. Results A total of 393 couples were enrolled for analysis; 156 (39.7%) were serodiscordant. The median relationship duration of serodiscordant couples was shorter than that of seroconcordant couples (6.4 years vs 11.6 years, p < 0.001). Of 237 HIV-infected partners, 17.7% had AIDS-defining illness, the median nadir CD4 count (interquartile range) was 240 (96–427) cells/mm3, 83.5% received antiretroviral therapy (ART), 98.3% had adherence > 95%, 90.3% had undetectable HIV RNA, and 22.9% had a prior history of treatment failure. There was no significant difference in condom usage in the prior 30 days between serodiscordant and seroconcordant couples. Factors of index HIV-infected patients associated with serodiscordant relationships were younger age (odds ratio [OR] 1.04 per 5 years; 95% confidence interval [CI] 1.01–1.06), receiving care at the general hospital (OR 1.73; 95% CI 1.08–2.78), a shorter duration of relationship (OR 1.04 per year; 95% CI 1.01–1.07), a higher nadir CD4 count (OR 1.06 per 50 cells/mm3; 95% CI 1.1–1.13), and not receiving a protease inhibitor-based regimen (OR 2.04; 95% CI 1.06–3.96). Conclusions A high number of serodiscordant couples was determined. Partners’ information should be retrieved as a holistic approach. Interventions for minimizing HIV transmission within serodiscordant couples should be evaluated and implemented.

Cardiac implantable electronic device infection in the cardiac referral center in Thailand: incidence, microbiology, risk factors, and outcomes

Despite the long experience of cardiac implantable electronic device (CIED) implantation in Thailand, epidemiology of CIED infection in Thailand has never been studied.