Ethnologue: Languages of the World

Geographical and genetic diversity of the human hepatitis B virus.

Ten hepatitis B virus (HBV) genotypes (A-J) and 34 HBV subgenotypes have been identified so far. HBV genotypes and subgenotypes have distinct geographical distributions, and have been shown to differ with regard to clinical outcome, prognosis, and response to interferon treatment. Infection with subgenotype A2 is frequently associated with high viral load, resulting in acute infection via horizontal transmission. Genotypes A and B are more sensitive to interferon treatment than genotypes D and C, respectively. Genotype B is more frequent in acute hepatitis than genotype C, whereas genotype C (C2) is more frequently associated with an increased risk of hepatocellular carcinoma (HCC), mostly cirrhotic, as compared with genotype B (B2). Genotype mixture is associated with high viral load and worse outcome of HBV infection. HBV mutations in the S genes, especially amino acids substitution at position 145 (G145R), are associated with immune escape, whereas mutations in the PreS or S genes which impair HBsAg secretion could present a risk to blood safety. HBV variants harboring mutations in the viral polymerase gene that confer resistance to nucleoside analogs may be selected during antiviral therapy. Different genotypes have distinct mutation patterns in the PreS and EnhII/BCP/Precore regions. PreS deletions, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC. HCC-associated HBV mutants may not transmit via mother-to-child transmission, and are likely generated during HBV-induced pathogenesis. Examination of HBV mutations alone or in combination and host genetic susceptibility will be helpful in classifying the HBV-infected subjects who will develop HCC and need active anti-viral treatments.

Clinical relevance and public health significance of hepatitis B virus genomic variations

The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.

Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions.

Hepatitis B and Hepatocellular Carcinoma.

The distribution of hepatitis B virus (HBV) in the populations of island Southeast Asia is of medical and anthropological interest and is associated with an unusually high genetic diversity. This study examined the association of this HBV genetic diversity with the ethnogeography of the populations of the Indonesian archipelago. Whole genome analysis of 21 HBV isolates from East Nusa Tenggara and Papua revealed two recently reported HBV/B subgenotypes unique to the former, B7 (7 isolates) and B8 (5 isolates), and uncovered a further novel subgenotype designated B9 (4 isolates). Further isolates were collected from 419 individuals with defined ethnic backgrounds representing 40 populations. HBV/B was predominant in Austronesian-language-speaking populations, whereas HBV/C was the major genotype in Papua and Papua-influenced populations of Moluccas; HBV/B3 was the predominant subgenotype in the western half of the archipelago (speakers of the Western Malayo-Polynesian [WMP] branch of Austronesian languages), whereas B7, B8 and B9 were specific to Nusa Tenggara (Central Malayo-Polynesian (CMP)). The result provides the first direct evidence that the distribution of HBV genotypes/subgenotypes in the Indonesian archipelago is related to the ethnic origin of its populations and suggests that the HBV distribution is associated with the ancient migratory events in the peopling of the archipelago.

https://link.springer.com/content/pdf/10.1007%2Fs00705-011-0926-y.pdf

Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9

The hepatitis B virus (HBV) genotype is associated with viral anthropological history, clinical outcome of disease and response to treatment. This study examines the HBV genotypes in Indonesia. HBV genotypes were determined by whole-genome sequencing and from the sequence of the Pre-S2 and S regions in a larger series. Two HBV genotypes, B (HBV/B) and C (HBV/C), were predominant. Three previously reported HBV/B subgenotypes were identified, with certain population association: HBV/B2 (HBV/Ba) was found mostly in Indonesians of Chinese ethnic origin, HBV/B3 was dominant among the Javanese, and HBV/B5, reported earlier from the Philippines, was also discovered, albeit at low frequency. Two other subgenotypes, HBV/B4 from Vietnam and HBV/B6, recently reported from the Arctic region, were not found. A novel subgenotype, HBV/B7, was recognized, associated with populations of the Nusa Tenggara islands in eastern Indonesia. Characteristic differences in HBsAg serotype and single nucleotide polymorphisms (SNPs) in the Pre-S2 region distinguish HBV/B7 from other HBV/B subgenotypes and further establish the new HBV subgenotype.

/pdf/genetic-study-of-hepatitis-b-virus-in-indonesia-reveals-a-3b44j82yv6.pdf

Genetic study of hepatitis B virus in Indonesia reveals a new subgenotype of genotype B in east Nusa Tenggara

Convalescent plasma therapy in patients with moderate-to-severe COVID-19: A study from Indonesia for clinical research in low- and middle-income countries.

The development of cell lines for the production of therapeutic protein drugs is complex, laborious, and expensive. However, due to the ever-increasing demand, the biomanufacturing process of recombinant proteins has to be steadily improved. Approaches that might be done to increase the production of biologics include continuous optimization, improvement of production, and better cell line development technology. Human erythropoietin (hEPO) is a hormone-like glycoprotein and has a molecular weight of 30,400 Daltons with 3 N-link glycosylation sites. hEPO is very essential and is a major factor in the formation of red blood cells. Decreased levels of hEPO in the body can cause anemia. This makes recombinant hEPO one of the most needed biologics in the world. With that in mind, this study aims to develop cell line capable of producing rhEPO with 2 additional N-links using CHO-DG44 cells. The cells were cultured in an orbital shaker at the speed of 130 rpm at 37oC and 5% CO2 condition and samples were taken on day 6. The results showed three clones, 193, 145, 223 with titer each of 2050+1.92, 1570+1.60 and 1320+1.90 milligrams/liter medium, respectively, with molecular weight of 40 - 50 kDa. 

Neni Nurainy

Papers

Ethnogeographical structure of hepatitis B virus genotype distribution in Indonesia and discovery of a new subgenotype, B9

Genetic study of hepatitis B virus in Indonesia reveals a new subgenotype of genotype B in east Nusa Tenggara

Convalescent plasma therapy in patients with moderate-to-severe COVID-19: A study from Indonesia for clinical research in low- and middle-income countries.

Cell line development for human erythropoietin with two additional N-links in CHO-DG44 cells