Lymph node remodelling underlies the attenuated form of HIV/AIDS in people with HIV-2

HIV-2 infection is associated with low-to-undetectable plasma viral load, broad and sustained specific antibody and T cell responses, and a slow course of CD4 T cell decline, even in the absence of antiretroviral therapy (ART). Here, we investigated the secondary lymphoid organs of people with HIV-2 (PWH2) as compared to people with HIV-1 (PWH1) and seronegative subjects. We found active HIV-2 replication and major disruption of lymph node architecture in PWH2, also attested by the alterations that we demonstrated in the blood counterparts of follicular T and B cells. These findings were corroborated by in vitro infection assays using tonsil organ cultures and HIV-2 or HIV-1 primary isolates with distinct co-receptor usage, CCR5 or CXCR4, which showed significant HIV-2 cytopathogenicity associated with post-transcriptional control of HIV-2 replication, revealed by high titres of cell-associated viral DNA and mRNA transcripts but reduced HIV-2 protein production. Overall, our findings support a major impact of HIV-2 on secondary lymphoid tissue organisation throughout the disease course, stressing the relevance of this neglected infection to understand host-pathogen equilibrium in retroviral zoonoses and to identify strategies towards a functional HIV cure.

Palavras-chave

HIV HIV-2 Lymph nodes Germinal centre T lymphocytes Virus replication

URI

http://hdl.handle.net/10400.26/63579

Citação

Susana M. Fernandes, Guilherme B. Farias, Ana R. Pires, Diana F. Santos, Ana Vieira Antão, André Pires, Rita Moura, Ana Godinho-Santos, Rita T. Marques, André MC Gomes, Cristina Ferreira, Helena Nunes-Cabaço, Perpétua Gomes, José Poças, Carlos Vasconcelos, Robert Badura, Ana E. Sousa, Lymph node remodelling underlies the attenuated form of HIV/AIDS in people with HIV-2, Journal of Infection, Volume 92, Issue 6, 2026, 106760, https://doi.org/10.1016/j.jinf.2026.106760

Editora

Elsevier

DOI

10.1016/j.jinf.2026.106760

Coleções

EM - Artigos Científicos

Licença CC

cclicense-by-nc-nd

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