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Substantial uneven proliferation of CD4+ T cells during recovery from acute HIV infection is sufficient to explain the observed expanded clones in the HIV reservoir.
Tettamanti Boshier, Florencia A; Reeves, Daniel B; Duke, Elizabeth R; Swan, David A; Prlic, Martin; Cardozo-Ojeda, E Fabian; Schiffer, Joshua T.
Afiliação
  • Tettamanti Boshier FA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA.
  • Reeves DB; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA.
  • Duke ER; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA.
  • Swan DA; Department of Medicine, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA.
  • Prlic M; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA.
  • Cardozo-Ojeda EF; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave., Seattle, WA, 98122, USA.
  • Schiffer JT; Department of Global Health, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA.
J Virus Erad ; 8(4): 100091, 2022 Dec.
Article em En | MEDLINE | ID: mdl-36582473
ABSTRACT
The HIV reservoir is a population of 1-10 million anatomically dispersed, latently infected memory CD4+ T cells in which HIV DNA is quiescently integrated into human chromosomal DNA. When antiretroviral therapy (ART) is stopped and HIV replication initiates in one of these cells, systemic viral spread resumes, rekindling progression to AIDS. Therefore, HIV latency prevents cure. The detection of many populations of identical HIV sequences at unique integration sites implicates CD4+ T cell proliferation as the critical driver of reservoir sustainment after a prolonged period of effective ART. Initial reservoir formation occurs during the first week of primary infection usually before ART is started. While empirical data indicates that both de novo infection and cellular proliferation generate latently infected cells during early untreated infection, it is not known which of these mechanisms is predominant. We developed a mathematical model that recapitulates the profound depletion and brisk recovery of CD4+ T cells, reservoir creation, and viral load trajectory during primary HIV infection. We extended the model to stochastically simulate individual HIV reservoir clones. This model predicts the first detection of HIV infected clones approximately 5 weeks after infection as has recently been shown in vivo and suggests that substantial, uneven proliferation among clones during the recovery from CD4+ lymphopenia is the most plausible explanation for the observed clonal reservoir distribution during the first year of infection.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2022 Tipo de documento: Article