HIV-1 and HIV-2 host interactions - - Lund University

• Karlsson I, Tingstedt JL, Sahin GÖ, Hansen M, Szojka Z, Buggert M, Biague A, Da Silva Z, Månsson F, Esbjörnsson J, Norrgren H, Medstrand P, Fomsgaard A*, and Jansson M*; Sweden-Guinea-Bissau Cohort Research Group. Cross-Reactive Antibodies With the Capacity to Mediate HIV-1 Envelope Glycoprotein-Targeted ADCC Identified in HIV-2-Infected Individuals. *Equal contributions. J Infect Dis. doi: 10.1093/ infdis/jiz001.

In this study we have in HIV-2-infected identified cross-reactive antibodies with the capacity to mediate HIV-1 Env-targeted ADCC. The magnitude of the cross-reactive ADCC depended on the origin of targeted HIV-1 Env and duration of infection. Thus, this suggests that preexisting antibodies triggered by HIV-2 might contribute to control of HIV-1 during dual infection.

• Esbjörnsson J, Jansson M, Jespersen S, Månsson F, Hønge BL, Lindman J, Medina C, da Silva ZJ, Norrgren H, Medstrand P, Rowland-Jones SL, Wejse C. HIV-2 as a model to identify a functional HIV cure. AIDS Res Ther. Review. 16 (1):24, 2019.

In this review we summaries different observations that collectively support HIV-2 as a model to identify a functional HIV cure.  

• Esbjörnsson J*, Månsson F*, Kvist A, da Silva ZJ, Andersson S, Fenyö EM, Isberg PE, Lindman J, Palm A, Jansson M, Medstrand P and Norrgren H. Sweden and Guinea-Bissau Cohort Research Group. Long follow-up reveals high proportions of HIV-2 related AIDS and mortality. *Equal contributions. Lancet HIV, pii: S2352-3018(18)30254-6, 2018.

It is clear that HIV-2 is more benign than HIV-1, however, reliable estimates of time to AIDS among those with HIV-2 have been lacking. In this study, with long-follow-up, 23 years, we show that also HIV-2-infected have a high probability of developing AIDS without treatment.

• Buggert M, Frederiksen J, Lund O, Biague A, Nielsen M, Tauriainen J, Norrgren H, Medstrand P, Karlsson A, and Jansson M; Sweden and Guinea-Bissau Cohort Research Group. CD4+ T type 1 cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection. AIDS 30:2415-25. 2016

By flow cytometry and advanced bioinformatics we reveal that CD4+ T cells with an activated /exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection. Thus, also HIV-2-infected without viremia may be eligible for antiretroviral treatment. Also for the first time, the CD4+ T cell phenotype of HIV-1, HIV-2 and dually infected is compared.

• Bächle SM*, Malone DFG*, Buggert M, Karlsson A, Isberg PE, Biague A, Norrgren H, Medstrand P, Moll M, Sandberg JK and Jansson M; Sweden and Guinea-Bissau Cohort Research Group. Elevated level of iNKT and NK cell activation correlates with disease progression in HIV-1 and HIV-2 infections. *Equal contributions. AIDS 30(11):1713-22. 2016

We show that disease progression, during HIV-1, HIV-2 and dual infections, is accompanied by NK cells with elevated activation. For the first time, we reveal that the same is true for iNKT cells. Thus, this highlights that HIV immunopathogenesis includes both iNKT and NK cells.

• Özkaya Sahin G, Holmgren B, da Silva  Z, Nielsen J, Nowroozalizadeh S,  Esbjörnsson J, Månsson F, Norrgren H, Aaby P, Fenyö EM, and Jansson M. Effect of complement on HIV-2 plasma antiviral activity is intratype-specific potent. J Virol. 87:273-81. 2013                

This study discloses that the effect of complement on HIV-2 plasma antiviral activity is intratype-specific and potent. Thus, antibody binding to HIV-2 Env structures facilitates efficient use of complement, and may contribute to HIV-2 immunity.

• Pawlowski A*, Jansson M*, Sköld M*, Rottenberg ME*, Källenius G. Tuberculosis and HIV co-infection. Review. *Equal contributions. PLoS Pathog. 8(2):e1002464. 2012.

Here we review recent development in the understanding of the interaction between Mtb and HIV during co-infection on cellular and organism level.

• Esbjörnsson J, Månsson F, Kvist A, Isberg PE, Nowroozalizadeh S, Biague AJ, Silva ZJ, Jansson M, Fenyö EM, Norrgren H and Medstrand P. Inhibition of HIV-1 disease progression by contemporaneous HIV-2 infection. N Engl J Med, 367:224-32, 2012

This study demonstrates that HIV-1 disease progression is inhibited by concomitant HIV-2 infection. The slower rate of disease progression was most evident during dual infection where HIV-2 preceded HIV-1 infection, a finding that suggests either cross-reactive immunity or other mechanisms of interference triggered by HIV-2.

• Fenyö EM, Esbjörnsson J, Medstrand P and Jansson M. HIV biological variation: from concept to clinical significance. J Intern Med. 270:520-31, 2011.

In this review we summarize studies, including our own, on HIV coreceptor interactions and the progress in understanding of the evolution, kinetics, and the proportions of HIV-1 populations able to use these receptors. Different aspects of the impact that these receptor interactions have on virus transmission, disease progression, and individualized treatment options, are described. 

• Nowroozalizadeh S, Månsson F, da Silva Z, Repits J, Dabo B, Pereira C, Biague A, Albert J, Nielsen J, Aaby P, Fenyö EM, Norrgren H, Holmgren B and Jansson M. Microbial translocation correlates to severity of both HIV-1 and HIV-2 infections. J Infect Dis 201:1150-4, 2010

We, for the first time, demonstrate that microbial translocation, i.e. LPS in plasma, is linked to severity of both HIV-1 and HIV-2 infections, and may contribute to immune activation. This despite the fact that HIV-2 infected individuals have lower plasma viral loads compared to HIV-1 infected.