Snapshot of HIV pathogenesis in China

Saksena, Nitin K.; Wang, Bin; Steain, Megan; Yang, Rong; Zhang, Lin Qi

doi:10.1038/sj.cr.7290373

Cited by 12 publications

(4 citation statements)

References 31 publications

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“…In 1994, the HIV epidemic entered a new phase involving spread outside of IDUs through transmission by female sex workers into the general population [4]. This phase of the HIV epidemic has been characterized by the appearance of numerous HIV strains, multiple subtypes, and circulating recombinant variants with the capacity for further recombination [5–7]. Understanding the emergence and spread of new HIV strains is important in meeting the challenges of HIV prevention and treatment posed by HIV diversity.…”

Section: Introductionmentioning

confidence: 99%

Update on diversity and distribution of HIV-1 subtypes in Yunnan province

Jia

et al. 2013

Epidemiol. Infect.

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The aim of this study was to characterize updated HIV subtypes in Yunnan to determine their origins and distribution within the population. RT-PCR of both the gag and env genes were sequenced from Yunnan province inhabitants newly diagnosed with HIV-1. Sequence data from 290 samples were used for statistical analysis of subtype distribution and phylogenetic tree construction. Distribution data were adjusted to account for different geographical distributions of HIV-1 subtypes in the population. Phylogenetic analysis revealed six HIV-1 subtypes in Yunnan, including eight types of unique recombination forms (URFs). The most prevalent subtypes in this province, CRF07_BC (18·9%), CRF08_BC (39·1%), CRF01_AE (22·4%), and URFs (subtype C, 5·9% and subtype B, 4·5%), were all recombinants. We found significant differences in the distribution of these HIV-1 subtypes not only geographically, but also between various ethnic groups and with respect to transmission routes. Our findings indicate a complex population of HIV-1 subtypes, URFs, and recombinant subtypes in Yunnan province. This diversity could make the prevention and control of HIV infection in Yunnan more difficult due to the possibility of virus recombination or infection by multiple subtypes.

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Section: Introductionmentioning

confidence: 99%

Update on diversity and distribution of HIV-1 subtypes in Yunnan province

Jia

et al. 2013

Epidemiol. Infect.

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“…With reference to two other equally important blood-borne pathogens, HBV and HIV-1, it is known that the former has shown a much higher prevalence than HCV in the general population in China (He et al, 2005), while the latter has now entered a generally disseminated stage (Saksena et al, 2005). Strikingly, no similar outbreaks of HBV and HIV-1 infections were observed in the same area and during the same period.…”

Section: Discussionmentioning

confidence: 99%

The evolutionary patterns of hepatitis C virus subtype 2a and 6a isolates linked to an outbreak in China in 2012

Lü

Zou

et al. 2015

Virology

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An HCV outbreak occurred in 2012 in China, affecting hundreds of patients. We characterized HCV subtype 2a and 6a sequences from 60 and 102 patients, respectively, and co-analyzed with 82 local controls and 103 calibrating references. The close grouping of the patients’ sequences contrasted sharply with the diversity of local controls. Scaled by the calibrating references, the emergence of patients’ isolates was estimated at 2–5 years before sampling. In contrast, the controls intermingled with the calibrating references that were much older. For both subtypes, the major and minor clusters could be defined, with the closeness to indicate linked transmission. Conclusion HCV sequences from the study patients grouped into three subtype 2a and two subtype 6a clusters, in addition to three 6a solitary branches, representing descendants of eight earlier strains that were distinct and otherwise sporadic. Due to iatrogenic transmission through reusing needles, five strains were highly selected and preferentially spread.

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“…Due to the enormous global economic, social, and health burdens of HIV-1/AIDS and despite the expanded availability of highly effective anti-retroviral drugs, the development of an efficacious prophylactic vaccine against HIV-1 remains a high priority, particularly among those populations hardest hit by the disease and with limited access to anti-viral drugs [ 3 ]. While subtype B is the major HIV-1 subtype in North America and Europe [ 4 ], it is also prevalent in other regions including Asia [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Generation and characterization of a bivalent protein boost for future clinical trials: HIV-1 subtypes CR01_AE and B gp120 antigens with a potent adjuvant

et al. 2018

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The RV144 Phase III clinical trial with ALVAC-HIV prime and AIDSVAX B/E subtypes CRF01_AE (A244) and B (MN) gp120 boost vaccine regime in Thailand provided a foundation for the future development of improved vaccine strategies that may afford protection against the human immunodeficiency virus type 1 (HIV-1). Results from this trial showed that immune responses directed against specific regions V1V2 of the viral envelope (Env) glycoprotein gp120 of HIV-1, were inversely correlated to the risk of HIV-1 infection. Due to the low production of gp120 proteins in CHO cells (2–20 mg/L), cleavage sites in V1V2 loops (A244) and V3 loop (MN) causing heterogeneous antigen products, it was an urgent need to generate CHO cells harboring A244 gp120 with high production yields and an additional, homogenous and uncleaved subtype B gp120 protein to replace MN used in RV144 for the future clinical trials. Here we describe the generation of Chinese Hamster Ovary (CHO) cell lines stably expressing vaccine HIV-1 Env antigens for these purposes: one expressing an HIV-1 subtype CRF01_AE A244 Env gp120 protein (A244.AE) and one expressing an HIV-1 subtype B 6240 Env gp120 protein (6240.B) suitable for possible future manufacturing of Phase I clinical trial materials with cell culture expression levels of over 100 mg/L. The antigenic profiles of the molecules were elucidated by comprehensive approaches including analysis with a panel of well-characterized monoclonal antibodies recognizing critical epitopes using Biacore and ELISA, and glycosylation analysis by mass spectrometry, which confirmed previously identified glycosylation sites and revealed unknown sites of O-linked and N-linked glycosylations at non-consensus motifs. Overall, the vaccines given with MF59 adjuvant induced higher and more rapid antibody (Ab) responses as well as higher Ab avidity than groups given with aluminum hydroxide. Also, bivalent proteins (A244.AE and 6240.B) formulated with MF59 elicited distinct V2-specific Abs to the epitope previously shown to correlate with decreased risk of HIV-1 infection in the RV144 trial. All together, these results provide critical information allowing the consideration of these candidate gp120 proteins for future clinical evaluations in combination with a potent adjuvant.

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Snapshot of HIV pathogenesis in China

Cited by 12 publications

References 31 publications

Update on diversity and distribution of HIV-1 subtypes in Yunnan province

Update on diversity and distribution of HIV-1 subtypes in Yunnan province

The evolutionary patterns of hepatitis C virus subtype 2a and 6a isolates linked to an outbreak in China in 2012

Generation and characterization of a bivalent protein boost for future clinical trials: HIV-1 subtypes CR01_AE and B gp120 antigens with a potent adjuvant

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