Dataset Information

Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4⁺ T cells measures viral sensitivity to broadly neutralizing antibodies.

ABSTRACT:

Importance

HIV-1 can efficiently transmit from one cell to another but accurate quantification of this mode of transmission is still challenging. Here, we developed an ultrasensitive assay to measure HIV-1 transmission between cells and to evaluate HIV-1 escape from broadly neutralizing antibodies in primary human T cells. This assay will contribute to understanding the fundamental mechanisms of HIV-1 cell-to-cell transmission, allow evaluation of pre-existing or acquired HIV-1 resistance in clinical trials, and can be adapted to study the biology of other retroviruses.

SUBMITTER: Mazurov D

PROVIDER: S-EPMC10790777 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4<sup>+</sup> T cells measures viral sensitivity to broadly neutralizing antibodies.

Mazurov Dmitriy D Herschhorn Alon A

mBio 20231208 1

<h4>Importance</h4>HIV-1 can efficiently transmit from one cell to another but accurate quantification of this mode of transmission is still challenging. Here, we developed an ultrasensitive assay to measure HIV-1 transmission between cells and to evaluate HIV-1 escape from broadly neutralizing antibodies in primary human T cells. This assay will contribute to understanding the fundamental mechanisms of HIV-1 cell-to-cell transmission, allow evaluation of pre-existing or acquired HIV-1 resistanc ...[more]

PMID: 38063394

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Project description:An increasing number of broadly neutralizing antibodies (bnAbs) are considered leads for HIV-1 vaccine development and novel therapeutics. Here, we systematically explored the capacity of bnAbs to neutralize HIV-1 prior to and post-CD4 engagement and to block HIV-1 cell-cell transmission. Cell-cell spread is known to promote a highly efficient infection with HIV-1 which can inflict dramatic losses in neutralization potency compared to free virus infection. Selection of bnAbs that are capable of suppressing HIV irrespective of the transmission mode therefore needs to be considered to ascertain their in vivo activity in therapeutic use and vaccines. Employing assay systems that allow for unambiguous discrimination between free virus and cell-cell transmission to T cells, we probed a panel of 16 bnAbs for their activity against 11 viruses from subtypes A, B and C during both transmission modes. Over a wide range of bnAb-virus combinations tested, inhibitory activity against HIV-1 cell-cell transmission was strongly decreased compared to free virus transmission. Activity loss varied considerably between virus strains and was inversely associated with neutralization of free virus spread for V1V2- and V3-directed bnAbs. In rare bnAb-virus combinations, inhibition for both transmission modes was comparable but no bnAb potently blocked cell-cell transmission across all probed virus strains. Mathematical analysis indicated an increased probability of bnAb resistance mutations to arise in cell-cell rather than free virus spread, further highlighting the need to block this pathway. Importantly, the capacity to efficiently neutralize prior to CD4 engagement correlated with the inhibition efficacy against free virus but not cell-cell transmitted virus. Pre-CD4 attachment activity proved strongest amongst CD4bs bnAbs and varied substantially for V3 and V1V2 loop bnAbs in a strain-dependent manner. In summary, bnAb activity against divergent viruses varied depending on the transmission mode and differed depending on the window of action during the entry process, underscoring that powerful combinations of bnAbs are needed for in vivo application.

Dataset Information

Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4⁺ T cells measures viral sensitivity to broadly neutralizing antibodies.

Importance

Publications

Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4<sup>+</sup> T cells measures viral sensitivity to broadly neutralizing antibodies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4+ T cells measures viral sensitivity to broadly neutralizing antibodies.

Importance

Publications

Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4<sup>+</sup> T cells measures viral sensitivity to broadly neutralizing antibodies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Ultrasensitive quantification of HIV-1 cell-to-cell transmission in primary human CD4⁺ T cells measures viral sensitivity to broadly neutralizing antibodies.