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  1. Angelopoulou E, Paudel YN, Papageorgiou SG, Piperi C
    ACS Chem Neurosci, 2021 08 04;12(15):2749-2764.
    PMID: 34275270 DOI: 10.1021/acschemneuro.1c00295
    Alzheimer's disease (AD) is the most common neurodegenerative disorder with obscure pathogenesis and no disease-modifying therapy to date. AD is multifactorial disease that develops from the complex interplay of genetic factors and environmental exposures. The E4 allele of the gene encoding apolipoprotein E (APOE) is the most common genetic risk factor for AD, whereas the E2 allele acts in a protective manner. A growing amount of epidemiological evidence suggests that several lifestyle habits and environmental factors may interact with APOE alleles to synergistically affect the risk of AD development. Among them, physical exercise, dietary habits including fat intake and ketogenic diet, higher education, traumatic brain injury, cigarette smoking, coffee consumption, alcohol intake, and exposure to pesticides and sunlight have gained increasing attention. Although the current evidence is inconsistent, it seems that younger APOE4 carriers in preclinical stages may benefit mostly from preventive lifestyle interventions, whereas older APOE4 noncarriers with dementia may show the most pronounced effects. The large discrepancies between the epidemiological studies may be attributed to differences in the sample sizes, the demographic characteristics of the participants, including age and sex, the methodological design, and potential related exposures and comorbidities as possible cofounding factors. In this Review, we aim to discuss available evidence of the prominent APOE genotype-environment interactions in regard to cognitive decline with a focus on AD, providing an overview of the current landscape in this field and suggesting future directions.
    Matched MeSH terms: Apolipoproteins E/genetics; Apolipoprotein E4/genetics
  2. Khan NA, Anwar A, Siddiqui R
    ACS Chem Neurosci, 2017 11 15;8(11):2355.
    PMID: 28933530 DOI: 10.1021/acschemneuro.7b00343
    Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent key priorities for improving outcomes from infections due to brain-eating amoebae.
    Matched MeSH terms: Acanthamoeba/genetics; Naegleria fowleri/genetics; Balamuthia mandrillaris/genetics
  3. Liew PS, Tan TH, Wong YC, Sim EUH, Lee CW, Narayanan K
    ACS Synth Biol, 2020 04 17;9(4):804-813.
    PMID: 32196315 DOI: 10.1021/acssynbio.9b00478
    TelN and tos are a unique DNA linearization unit isolated from bacteriophage N15. While being transferable, the TelN cleaving-rejoining activities remained stable to function on tos in both bacterial and mammalian environments. However, TelN contribution in linear plasmid replication in mammalian cells remains unknown. Herein, we investigated the association of TelN in linear tos-containing DNA (tos-DNA) replication in mammalian cells. Additionally, the mammalian origin of replication (ori) that is well-known to initiate the replication event of plasmid vectors was also studied. In doing so, we identified that both TelN and mammalian initiation sites were essential for the replication of linear tos-DNA, determined by using methylation sensitive DpnI/MboI digestion and polymerase chain reaction (PCR) amplification approaches. Furthermore, we engineered the linear tos-DNA to be able to retain in mammalian cells using S/MAR technology. The resulting S/MAR containing tos-DNA was robust for at least 15 days, with (1) continuous tos-DNA replication, (2) correct splicing of gene transcripts, and (3) stable exogenous gene expression that was statistically comparable to the endogenous gene expression level. Understanding the activities of TelN and tos in mammalian cells can potentially provide insights for adapting this simple DNA linearization unit in developing novel genetic engineering tools, especially to the eukaryotic telomere/telomerase study.
    Matched MeSH terms: Bacteriophages/genetics; DNA Replication/genetics*; DNA, Viral/genetics; Enzyme Precursors/genetics*; Plasmids/genetics; Viral Proteins/genetics*; Telomerase/genetics*; Matrix Attachment Regions/genetics
  4. Wong YC, Ng AWR, Chen Q, Liew PS, Lee CW, Sim EUH, et al.
    ACS Synth Biol, 2023 Apr 21;12(4):909-921.
    PMID: 37026178 DOI: 10.1021/acssynbio.2c00580
    Bacteriophage N15 is the first virus known to deliver linear prophage into Escherichia coli. During its lysogenic cycle, N15 protelomerase (TelN) resolves its telomerase occupancy site (tos) into hairpin telomeres. This protects the N15 prophage from bacterial exonuclease degradation, enabling it to stably replicate as a linear plasmid in E. coli. Interestingly, purely proteinaceous TelN can retain phage DNA linearization and hairpin formation without involving host- or phage-derived intermediates or cofactors in the heterologous environment. This unique feature has led to the advent of synthetic linear DNA vector systems derived from the TelN-tos module for the genetic engineering of bacterial and mammalian cells. This review will focus on the development and advantages of N15-based novel cloning and expression vectors in the bacterial and mammalian environments. To date, N15 is the most widely exploited molecular tool for the development of linear vector systems, especially the production of therapeutically useful miniDNA vectors without a bacterial backbone. Compared to typical circular plasmids, linear N15-based plasmids display remarkable cloning fidelity in propagating unstable repetitive DNA sequences and large genomic fragments. Additionally, TelN-linearized vectors with the relevant origin of replication can replicate extrachromosomally and retain transgenes functionality in bacterial and mammalian cells without compromising host cell viability. Currently, this DNA linearization system has shown robust results in the development of gene delivery vehicles, DNA vaccines and engineering mammalian cells against infectious diseases or cancers, highlighting its multifaceted importance in genetic studies and gene medicine.
    Matched MeSH terms: Genetic Vectors/genetics; Mammals/genetics; Plasmids/genetics; Prophages/genetics
  5. Yong YK, Shankar EM, Solomon A, Spelman T, Fairley CK, Elliott JH, et al.
    AIDS, 2016 09 10;30(14):2159-68.
    PMID: 27281059 DOI: 10.1097/QAD.0000000000001179
    BACKGROUND: Chronic HIV infection leads to marked depletion of CD4 T cells in the gastrointestinal tract and increased microbial translocation measured by an increase in circulating lipopolysaccharide (LPS) levels. Here, we hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor 4 (TLR4) and CD14, the principal receptors for LPS, were associated with CD4 T-cell recovery postantiretroviral therapy (ART).

    METHODS: Prospective study of predominantly white HIV-infected participants receiving suppressive ART for at least 12 months. We analysed the CD14 SNPs C-260T and the TLR4 SNPs A+896G, C+1196T. We also determined the levels of LPS and soluble CD14 in plasma samples collected pre-ART and post-ART initiation. CD4 T-cell recovery was assessed by linear mixed models.

    RESULTS: Following ART, individuals with a TT genotype compared with a CT or CC genotype for CD14 C-260T SNP showed higher levels of soluble CD14 (P = 0.008 and 0.003, respectively). The CC genotype for the CD14 C-260T SNP, compared with CT or TT, and the TLR4 SNP (AC/GT), compared with the homozygous genotype (AA/CC), were both independently associated with enhanced long-term CD4 T-cell recovery (>3 months; P 

    Matched MeSH terms: Antigens, CD14/genetics*; Toll-Like Receptor 4/genetics*
  6. Tee KK, Pon CK, Kamarulzaman A, Ng KP
    AIDS, 2005 Jan 28;19(2):119-26.
    PMID: 15668536
    OBJECTIVES: To investigate the molecular epidemiology of HIV-1 and to screen for the emergence of intersubtype recombinants in Kuala Lumpur, Malaysia.

    DESIGN: A molecular epidemiology study was conducted among HIV-1 seropositive patients attending the University Malaya Medical Center (UMMC) from July 2003 to June 2004.

    METHODS: Protease (PR) and reverse transcriptase (RT) gene sequences were derived from drug resistance genotyping assay of 100 newly diagnosed or antiretroviral-naive patients. These were phylogenetically analysed to determine the subtypes and recombination breakpoint analyses were performed on intersubtype recombinants to estimate the recombination breakpoint(s).

    RESULTS: CRF01_AE predominated in Kuala Lumpur with 65% in both PR and RT genes. B subtype was detected at 14% and 12% in PR and RT genes, respectively. C subtype was present at 1% in both genes. Overall, the concordance of PR and RT genes in discriminating subtypes/circulating recombinant forms (CRF) was high at 96%. In this study, novel CRF01_AE/B intersubtype recombinants were detected at high prevalence (22%), including those isolates with subtype discordance. Thai variants of CRF01_AE and B subtype were involved in the genesis of these unique recombinant forms (URF). Interestingly, 19 CRF01_AE/B intersubtype recombinant isolates shared similar recombination breakpoints in both PR and RT genes. Several distinct URF were also identified.

    CONCLUSION: PR and RT genes can be utilized for subtype/CRF assessment with high degree of agreement, allowing concurrent surveillance of circulating HIV-1 subtypes with antiretroviral drug resistance genotyping tests. The emergence of highly identical CRF01_AE/B intersubtype recombinants suggests the possibility of the appearance of a new circulating recombinant form in Kuala Lumpur.

    Matched MeSH terms: HIV Seropositivity/genetics*; Peptide Hydrolases/genetics; Recombination, Genetic/genetics*; RNA, Viral/genetics; HIV-1/genetics*; HIV Reverse Transcriptase/genetics
  7. Weniger BG, Takebe Y, Ou CY, Yamazaki S
    AIDS, 1994;8 Suppl 2:S13-28.
    PMID: 7857556
    Matched MeSH terms: HIV/genetics*
  8. Yunihastuti E, Teeratakulpisarn N, Jeo WS, Nilasari H, Rachmadi L, Somia IKA, et al.
    AIDS, 2020 11 01;34(13):1933-1941.
    PMID: 32773478 DOI: 10.1097/QAD.0000000000002654
    OBJECTIVES: Persistent anal high-risk human papillomavirus (HR-HPV) infection is a major risk factor for anal cancer among MSM and transgender women (TGW). We aimed to estimate incidence, clearance, and persistence of anal HR-HPV in HIV-positive and HIV-negative MSM and TGW, and to assess factors for HR-HPV persistence.

    DESIGN: Prospective cohort study.

    METHODS: MSM and TGW aged at least 18 years, were enrolled from Indonesia, Malaysia, and Thailand, then followed up 6-monthly for 12 months. Anal swabs were collected at every visit for HR-HPV genotypes to define anal HR-HPV incidence, clearance, and persistence. Logistic regression was used to evaluate factors associated with HR-HPV persistence.

    RESULTS: Three hundred and twenty-five MSM and TGW were included in this study, of whom 72.3% were HIV-positive. The incidence of anal HR-HPV persistence was higher in HIV-positive than HIV-negative MSM participants (28.4/1000 vs. 13.9/1000 person-months). HIV-positive participants had HR-HPV lower clearance rate than HIV-negative participants (OR 0.3; 95% CI 0.1-0.7). The overall persistence of HR-HPV was 39.9% in HIV-positive and 22.8% HIV-negative participants. HPV-16 was the most persistent HR-HPV in both HIV-positive and HIV-negative participants. HIV infection (aOR 2.87; 95% CI 1.47-5.61), living in Kuala Lumpur (aOR 4.99; 95% CI 2.22-11.19) and Bali (aOR 3.39; 95% CI 1.07-10.75), being employed/freelance (aOR 3.99; 95% CI 1.48-10.77), and not being circumcised (aOR 2.29; 95% CI 1.07-4.88) were independently associated with anal HR-HPV persistence.

    CONCLUSION: HIV-positive MSM and TGW had higher risk of persistent anal HR-HPV infection. Prevention program should be made available and prioritized for HIV-positive MSM and TGW where resources are limited.

    Matched MeSH terms: Papillomaviridae/genetics
  9. Cassol S, Weniger BG, Babu PG, Salminen MO, Zheng X, Htoon MT, et al.
    AIDS Res Hum Retroviruses, 1996 Oct 10;12(15):1435-41.
    PMID: 8893051
    Global surveillance of HIV-1 subtypes for genetic characterization is hampered by the biohazard of processing and the difficulties of shipping whole blood or cells from many developing country regions. We developed a technique for the direct automated sequencing of viral DNA from dried blood spot (DBS) specimens collected on absorbent paper, which can be mailed unrefrigerated in sturdy paper envelopes with low biohazard risk. DBS were collected nonrandomly from HIV-1-infected, mostly asymptomatic, patients in five Asian countries in 1991, and shipped via airmail or hand carried without refrigeration to Bangkok, and then transshipped to North America for processing. After more than 2 years of storage, including 6 months at ambient temperatures, proviral DNA in the DBS was amplified by nested PCR, and a 389-nucleotide segment of the C2-V3 env gene region was sequenced, from which 287 base pairs were aligned and subtyped by phylogenetic analysis with neighbor-joining and other methods. From southern India, there were 25 infections with subtype C and 2 with subtype A. From Myanmar (Burma), we identified the first subtype E infection, as well as six subtype BB, a distinct cluster within subtype B that was first discovered in Thailand and that has now appeared in China, Malaysia, and Japan. From southwest China, one BB was identified, while a "classical" B typical of North American and European strains was found in Indonesia. From Thailand, five DBS of ambiguous serotype were identified as three B, one BB, and one E. A blinded control serotype E specimen was correctly identified, but a serotype BB control was not tested. Most HIV-1 in southern India appears to be env subtype C, with rare A, as others have reported in western and northern India. The subtypes BB and E in Myanmar, and the BB in China, suggest epidemiological linkage with these subtypes in neighboring Thailand. DBS are a practical, economical technique for conducting large-scale molecular epidemiological surveillance to track the global distribution and spread of HIV-1 variants.
    Matched MeSH terms: HIV-1/genetics*
  10. Lam EP, Moore CL, Gotuzzo E, Nwizu C, Kamarulzaman A, Chetchotisakd P, et al.
    AIDS Res Hum Retroviruses, 2016 09;32(9):841-50.
    PMID: 27346600 DOI: 10.1089/AID.2015.0331
    We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p  .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01_AE (n = 109, 22%), G (n = 25, 5%), and CRF02_AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p 
    Matched MeSH terms: HIV-1/genetics
  11. SahBandar IN, Takahashi K, Motomura K, Djoerban Z, Firmansyah I, Kitamura K, et al.
    AIDS Res Hum Retroviruses, 2011 Jan;27(1):97-102.
    PMID: 20958201 DOI: 10.1089/aid.2010.0163
    Cocirculation of subtype B and CRF01_AE in Southeast Asia has led to the establishment of new recombinant forms. In our previous study, we found five samples suspected of being recombinants between subtype B and CRF01_AE, and here, we analyzed near full-length sequences of two samples and compared them to known CRFs_01B, subtype B, and CRF01_AE. Five overlapped segments were amplified with nested PCR from PBMC DNA, sequenced, and analyzed for genome mosaicism. The two Indonesian samples, 07IDJKT189 and 07IDJKT194, showed genome-mosaic patterns similar to CRF33_01B references from Malaysia, with one short segment in the 3' end of the p31 integrase-coding region, which was rather more similar to subtype B than CRF01_AE, consisting of unclassified sequences. These results suggest gene-specific continuous diversification and spread of the CRF33_01B genomes in Southeast Asia.
    Matched MeSH terms: RNA, Viral/genetics*; HIV-1/genetics*
  12. Tee KK, Kamarulzaman A, Ng KP
    AIDS Res Hum Retroviruses, 2006 Feb;22(2):121-4.
    PMID: 16478392
    To assess the prevalence of mutations associated with drug resistance in antiretroviral-naive patients in Kuala Lumpur, Malaysia, genotypic resistance testing was conducted among drug-naive HIV-1 patients attending the University Malaya Medical Center (UMMC) between July 2003 and June 2004. Reverse transcriptase (RT) and protease genes of plasma virions were sequenced from 100 individuals. The majority of the patients were recently diagnosed. Codons 20-255 of the RT and 1-96 of the protease gene were examined for major and minor mutations associated with antiretroviral resistance reported by the International AIDS Society- USA (IAS-USA) Drug Resistance Mutations Group. The prevalence of patients with at least one major mutation conferring drug resistance was 1%, with only one patient having a Y181C amino acid substitution in the RT gene that confers high-level resistance to nevirapine and delavirdine. Minor mutations were detected in high prevalence in the protease gene. Amino acid substitutions I13V, E35D, and M36I were associated with CRF01_AE while L63P, V77I, and I93L were associated with subtype B. Baseline prevalence of major mutations associated with resistance to antiretroviral drugs was low among antiretroviral-naive HIV-1 patients, suggesting that routine drug resistance testing may be unnecessary for all individuals newly diagnosed with HIV or all patients beginning antiretroviral therapy.
    Matched MeSH terms: RNA, Viral/genetics; HIV-1/genetics*; HIV Protease/genetics; Drug Resistance, Viral/genetics*; HIV Reverse Transcriptase/genetics
  13. Tee KK, Saw TL, Pon CK, Kamarulzaman A, Ng KP
    AIDS Res Hum Retroviruses, 2005 Dec;21(12):1046-50.
    PMID: 16379608
    Earlier studies in the 1990s indicate that human immunodeficiency virus type 1 (HIV-1) subtype B has been the predominant subtype among injecting drug users (IDUs) in Malaysia. More recent studies performed between 2003 and 2004, however, show a high prevalence of unique CRF01_AE/B intersubtype recombinants among IDUs. To determine the subtype distribution among IDUs in Kuala Lumpur prior to the emergence of CRF01_AE/B intersubtype recombinants, the gag-pol or the reverse transcriptase gene was sequenced from IDUs who were diagnosed as HIV positive between 1993 and 2002. Subtype B was present at 50.0% followed by CRF01_AE/B recombinant at 41.7%, with more CRF01_AE/B recombinants detected between 2000 and 2002. All CRF01_AE/B recombinants shared similar recombination patterns. Interestingly, we found that this potential new candidate of circulating recombinant form (CRF) could have emerged as early as the mid-1990s. The results showed evidence of changing HIV-1 molecular epidemiology toward the predominance of CRF01_AE/B intersubtype recombinants among IDUs in Kuala Lumpur.
    Matched MeSH terms: HIV-1/genetics*; Gene Products, gag/genetics; Gene Products, pol/genetics
  14. Sahbandar IN, Takahashi K, Djoerban Z, Firmansyah I, Naganawa S, Motomura K, et al.
    AIDS Res Hum Retroviruses, 2009 Jul;25(7):637-46.
    PMID: 19621986 DOI: 10.1089/aid.2008.0266
    HIV infection is a major problem in Indonesia. The number of people living with HIV has been increasing from year to year, especially among injecting drug users (IDUs). Since there were only limited data about molecular epidemiology profiles of HIV/AIDS in Indonesia, a cross-sectional study involving 208 HIV-1-seropositive individuals was conducted in 2007 in Jakarta. The majority of participants were 16-30 years of age (64.9%) and 74.5% were male. The most frequent risk factor was injecting drug use (IDU) (45.7%) followed by heterosexual transmission (34.1%). Phylogenetic analysis of gag (p17 and p6) and env C2V3 regions showed 200 (96.2%) of 208 DNA samples were CRF01_AE and only 3 (1.4%) were subtype B. Five samples (2.4%) indicated discordant subtypes between the three aforementioned regions: three of them showed unique CRF01_AE/B recombination patterns in 2.3-kbp nucleotide sequences (from p17 to part of RT), including one sample showing similarity to CRF33_01B, reported previously in Malaysia. This study shows the current predominant subtype is CRF01_AE in every risk group, with a decreasing number of pure subtype B, and the first identification of CRF01_AE/B recombinant forms among HIV-1-seropositive Indonesians.
    Matched MeSH terms: DNA, Recombinant/genetics*; DNA, Viral/genetics; HIV-1/genetics*; HIV Infections/genetics
  15. Lau KA, Wang B, Kamarulzaman A, Ng KP, Saksena NK
    AIDS Res Hum Retroviruses, 2007 Sep;23(9):1139-45.
    PMID: 17919110
    A new HIV-1 circulating recombinant form (CRF), CRF33_01B, has been identified in Malaysia. Concurrently we found a unique recombinant form (URF), that is, the HIV-1 isolate 06MYKLD46, in Kuala Lumpur, Malaysia. It is composed of B or a Thai variant of the B subtype (B') and CRF01_AE. Here, we determined the near full-length genome of the isolate 06MYKLD46 and performed detailed phylogenetic and bootscanning analyses to characterize its mosaic composition and to further confirm the subtype assignments. Although the majority of the 06MYKLD46 genome is CRF01_AE, we found three short fragments of B or B' subtype inserted along the genome. These B or B' subtype regions were 716 and 335 bp, respectively, in the protease-reverse transcriptase (PR-RT) region, similar to those found in CRF33_01B, as well as an extra 590 bp in the env gene region. Thus we suggest that 06MYKLD46 is a possible second-generation HIV-1 recombinant derived from CRF33_01B.
    Matched MeSH terms: HIV-1/genetics
  16. Kasper P, Chalwatzis N, Duraisamy G, Ofenloch-Hähnle B, Faatz E
    AIDS Res Hum Retroviruses, 1997 Sep 20;13(14):1251-3.
    PMID: 9310293
    Matched MeSH terms: HIV-1/genetics*; HIV Infections/genetics*; Gene Products, gag/genetics*; Substance Abuse, Intravenous/genetics*
  17. Beyrer C, Vancott TC, Peng NK, Artenstein A, Duriasamy G, Nagaratnam M, et al.
    AIDS Res Hum Retroviruses, 1998 Dec 20;14(18):1687-91.
    PMID: 9870323
    We investigated the molecular epidemiology of HIV-1 subtypes in Malaysia among injecting drug users (IDUs) and sexual transmission risk groups, using serologic and genetic techniques. Frozen sera collected at a general hospital, a blood bank, several drug treatment centers, and an STD clinic in Kuala Lumpur, between 1992 and 1996, were investigated retrospectively. V3 peptide serotyping and monomeric gp120 capture serotyping were used to study 89 known HIV-1-infected subjects. The methods differentiate subtypes B, E, and C. V3 peptide and gp120 capture results were comparable. No subtype C-specific reactive sera were found; one specimen was dually reactive for subtypes C and B, using the V3 peptide ELISA; and four were durally reactive for subtypes E and C using this assay. Genotypic analysis of HIV-1 gag RNA in serum was done on a subset of subjects and confirmed serologic findings. HIV-1 subtypes differed significantly by risk category: of 53 IDUs, 29 (55%) were infected with subtype B and 19 (36%) were infected with subtype E, 3 (6%) were dually reactive, and 2 (4%) were not typable. Of 36 persons with heterosexual risks, 29 (81%) were infected with subtype E, 5 (14%) were infected with subtype B, and 2 (5%) were not typable. Persons with IDU risks were significantly more likely to be infected with subtype B than were those with sexual risks (OR 5.89; 95% CI, 1.94-18.54; p < 0.001). Subtypes B and E of HIV-1 appear to predominate in Malaysia; subtype B was more prevalent among IDUs; subtype E was more prevalent among all other groups. These results may have important HIV-1 vaccine implications.
    Matched MeSH terms: HIV-1/genetics*
  18. Brown TM, Robbins KE, Sinniah M, Saraswathy TS, Lee V, Hooi LS, et al.
    AIDS Res Hum Retroviruses, 1996 Nov 20;12(17):1655-7.
    PMID: 8947304
    Matched MeSH terms: Peptide Fragments/genetics*; HIV-1/genetics*; HIV Envelope Protein gp120/genetics*
  19. Ou W, Li K, Feng Y, Huang Q, Ge Z, Sun J, et al.
    AIDS Res Hum Retroviruses, 2019 04;35(4):414-418.
    PMID: 30229664 DOI: 10.1089/AID.2018.0197
    To date, there are 16 types of CRF01_AE/B circulating recombinant forms identified, and most of them are distributed in Asian countries such as China, Malaysia, and Singapore. Previous HIV molecular epidemiological surveys showed that CRF01_AE (27.6%) and B (9.6%) subtypes are predominant strains in mainland of China. At the same time, the HIV-1 virus spreads faster in the men who have sex with men (MSM) population than in other risk groups. In Shanghai district, ∼66.0% of newly reported cases were infected through homosexual transmission. In this study, we report a novel recombinant strain of CRF01_AE/B. The near full-length genome phylogenetic tree showed that the strain clustered with the CRF01_AE reference sequence and placed in the peripheral position within the branch of the CRF01_AE strain. Subregional evolutionary results indicated that the CRF01_AE subtype was derived from cluster 4 of CRF01_AE, which is mainly distributed in northern China. The subtype B was correlated with the U.S./Europe B, which are widely prevalent in the Chinese MSM population. In recent years, a large number of recombinant forms between CRF01_AE and B strains are continuously emerging in China. Therefore, understanding the current epidemic recombinant forms will have significant implications for prevention and treatment of HIV/AIDS.
    Matched MeSH terms: HIV-1/genetics*
  20. Ng QR, Tee KK, Binley JM, Tong T
    AIDS Res Hum Retroviruses, 2022 Feb;38(2):162-172.
    PMID: 34006141 DOI: 10.1089/AID.2020.0299
    Human immunodeficiency virus type-1 (HIV-1) antigenic variation poses a great challenge for vaccine immunogen design to elicit broadly neutralizing antibodies (bNAbs). Over the last 10-15 years, great progress has been made to understand the conserved sites of sensitivity on HIV envelope glycoprotein spikes targeted by bNAbs. Plasma neutralization mapping and monoclonal antibody isolation efforts have revealed five major conserved epitope clusters. Most of this work has focused on subtype B and C-infected Caucasian or African donors. It is not clear if the same epitopes and epitope rank order preferences are also true in donors infected with different HIV-1 subtypes and with different racial backgrounds. To investigate this point, in this study we report the first attempt to profile the bNAb specificities of CRF01_AE-infected Malaysian plasmas. We first measured neutralization titers of 21 plasmas against a subtype A, B, and AE pseudovirus panel. This revealed that 14% (3 of 21) plasmas had cross-clade breadth. Focusing on the cross-neutralizing plasma P9, we used AE and JR-FL mutant pseudoviruses, gp120 monomer interference, and native polyacrylamide gel electrophoresis to better understand the neutralization specificity. P9 demonstrates CD4-binding-site specificity with trimer dependence and D368 independence.
    Matched MeSH terms: HIV Envelope Protein gp120/genetics; env Gene Products, Human Immunodeficiency Virus/genetics
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