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An in vitro dataset on infectious potential of transmitted/founder (TF) and non-TF (NT) HIV-1 viruses generated from Interferon alpha-treated primary CD4+ T cells.

ABSTRACT: This data article describes the infectivity of transmitted/founder (TF) and non-TF (NT) HIV-1 viruses derived from primary CD4+ T cells treated with or without IFN-?, over a period of 12 days. TF and NT viruses described in this article were derived from the same individual (one of each from 8 infants who acquired HIV infection through mother-to-child transmission (MTCT). IFN-? resistance to both TF and NT viruses was studied by infecting TZM-bl cells and measuring luciferase expression (expressed as relative light units, RLU). Measurement of luciferase expression is extremely sensitive and allows quantification of even small changes in gene expression at the transcriptional level.

SUBMITTER: Ashokkumar M

PROVIDER: S-EPMC7075791 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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An in vitro dataset on infectious potential of transmitted/founder (TF) and non-TF (NT) HIV-1 viruses generated from Interferon alpha-treated primary CD4+ T cells.

Ashokkumar Manickam M Sonawane Aanand A Sathiyamani Balakumaran B Esakialraj L Bennett Henzeler BH Hanna Luke Elizabeth LE

Data in brief 20200229

This data article describes the infectivity of transmitted/founder (TF) and non-TF (NT) HIV-1 viruses derived from primary CD4+ T cells treated with or without IFN-α, over a period of 12 days. TF and NT viruses described in this article were derived from the same individual (one of each from 8 infants who acquired HIV infection through mother-to-child transmission (MTCT). IFN-α resistance to both TF and NT viruses was studied by infecting TZM-bl cells and measuring luciferase expressi ...[more]

PMID: 32195300

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Project description:Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-Nef?gp120 to obtain chimeric viruses. Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection. Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C. The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies. Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants. The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection. CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses. The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.IMPORTANCE Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist. One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus. Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet. An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV. Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.

Project description:UnlabelledThe interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8(+) T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8(+) T cell responses has been quantified for the first time in the early phase of primary HCV infection. These rapid escape dynamics were associated with higher-magnitude CD8(+) T cell responses. These findings raise questions regarding optimal selection of immunogens for HCV vaccine development and suggest that detailed analysis of individual epitopes may be required.ImportanceA major limitation in our detailed understanding of the role of immune response in HCV clearance has been the lack of data on very early primary infection when the transmitted viral variants successfully establish the acute infection. This study was made possible through the availability of specimens from a unique cohort of asymptomatic primary infection cases in whom the first available viremic samples were collected approximately 3 weeks postinfection and at regular intervals thereafter. The study included detailed examination of both the evolution of the viral population and the host cellular immune responses against the T/F viruses. The findings here provide the first evidence of host cellular responses targeting T/F variants and imposing a strong selective force toward viral escape. The results of this study provide useful insight on how virus escapes the host response and consequently on future analysis of vaccine-induced immunity.

Dataset Information

An in vitro dataset on infectious potential of transmitted/founder (TF) and non-TF (NT) HIV-1 viruses generated from Interferon alpha-treated primary CD4+ T cells.

Publications

An <i>in</i> <i>vitro</i> dataset on infectious potential of transmitted/founder (TF) and non-TF (NT) HIV-1 viruses generated from Interferon alpha-treated primary CD4<sup>+</sup> T cells.

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