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Transmission dynamics of HIV-1 subtype B strains in Indonesia.

ABSTRACT: Human immunodeficiency virus type 1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) represent a major public health concern in Indonesia. Although circulating recombinant form (CRF) 01_AE is a predominant subtype in Indonesia, HIV-1 subtype B (HIV-1B) is also widely prevalent. However, the viral genetic evolution, spatial origins, and patterns of transmission of HIV-1B in Indonesia remain unclear. In the present study, we described the evolutionary characteristics and spatial-temporal transmission networks of HIV-1B in Indonesia. To elucidate the epidemiological link between HIV-1B epidemics in Indonesia and those in the remainder of the world, we conducted phylogenetic analyses of HIV-1B strains in Indonesia. Based on the results obtained, at least three epidemic clades [the Indonesia, United States (US), and China clades] of HIV-1B were found to be prevalent in Indonesia. In order to identify the potential source and transmission route of Indonesian HIV-1B strains, we performed Bayesian analyses and constructed Maximum clade credibility trees of each clade. Although some HIV-1B strains in Indonesia were introduced from Thailand, the prevalent HIV-1B strains appeared to have been directly introduced from Europe or America. Indonesian HIV-1B may have spread via the main dispersal of pandemic HIV-1B strains via the US from the Caribbean region rather than being directly introduced from Africa.

SUBMITTER: Ueda S

PROVIDER: S-EPMC6764962 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Transmission dynamics of HIV-1 subtype B strains in Indonesia.

Ueda Shuhei S Witaningrum Adiana Mutamsari AM Khairunisa Siti Qamariyah SQ Kotaki Tomohiro T Motomura Kazushi K Nasronudin Kameoka Masanori M

Scientific reports 20190927 1

Human immunodeficiency virus type 1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) represent a major public health concern in Indonesia. Although circulating recombinant form (CRF) 01_AE is a predominant subtype in Indonesia, HIV-1 subtype B (HIV-1B) is also widely prevalent. However, the viral genetic evolution, spatial origins, and patterns of transmission of HIV-1B in Indonesia remain unclear. In the present study, we described the evolutionary characteristics and spatial-temporal tran ...[more]

PMID: 31562375

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Project description:IntroductionThe human immunodeficiency virus 1 (HIV-1) pandemic is characterized by numerous distinct sub-epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV-1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV-1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW-specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi-Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2-fold increase in the number of NSW-specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above-average growth rate (>1.5 sequences / 6-months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.

Project description:HIV-1 downregulates HLA-A and HLA-B from the surface of infected cells primarily to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface and bind inhibitory killer immunoglobulin-like receptors, preventing NK cell-mediated suppression. However, a recent study found HIV-1 primary viruses have the capacity to downregulate HLA-C. The goal of this study was to assess the heterogeneity of HLA-A, HLA-B and HLA-C downregulation among full-length primary viruses from six chronically infected and six newly infected individuals from transmission pairs, and to determine whether transmitted/founder variants exhibit common HLA class I downregulation characteristics. We measured HLA-A, HLA-B, HLA-C and total HLA class I downregulation by flow cytometry of primary CD4 T cells infected with 40 infectious molecular clones. Primary viruses mediated a range of HLA class I downregulation capacities (1.3-6.1-fold), which could differ significantly between transmission pairs. Downregulation of HLA-C surface expression on infected cells correlated with susceptibility to in vitro NK cell suppression of virus release. Despite this, transmitted/founder variants did not share a common downregulation signature and instead were more similar to the quasispecies of matched donor partners. These data indicate that a range of viral abilities to downregulate HLA-A, HLA-B and HLA-C exist within and between individuals, which can have functional consequences on immune recognition.IMPORTANCE Subtype C HIV-1 is the predominant subtype involved in heterosexual transmission in Sub-Saharan Africa. Authentic subtype C viruses that contain natural sequence variations throughout the genome are often not used in experimental systems, due to technical constraints and sample availability. In this study, authentic full-length subtype C viruses, including transmitted/founder viruses, were examined for the ability to disrupt surface expression of human leukocyte antigen (HLA) class I molecules, which are central to both adaptive and innate immune responses to viral infections. We found that HLA class I downregulation capacity of primary viruses varied, and HLA-C downregulation capacity impacted viral suppression by natural killer cells. Transmitted viruses were not distinct in the capacity for HLA class I downregulation or natural killer cell evasion. These results enrich our understanding of the phenotypic variation existing among natural HIV-1 viruses, and how that might impact the ability of the immune system to recognize infected cells in acute and chronic infection.

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Transmission dynamics of HIV-1 subtype B strains in Indonesia.

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Transmission dynamics of HIV-1 subtype B strains in Indonesia.

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