# Sex‐Specific Factors Influencing HIV Infection

**Authors:** Maria Pujantell, Marcus Altfeld

PMC · DOI: 10.1111/imr.70109 · Immunological Reviews · 2026-02-20

## TL;DR

This paper reviews how sex-specific factors like genes and hormones influence immune responses to HIV-1 and affect disease outcomes.

## Contribution

The paper provides a review of how X/Y-chromosome genes and sex hormones modulate HIV-1 antiviral immunity.

## Key findings

- X- and Y-chromosome-encoded genes influence antiviral immune responses.
- Sex steroid hormones modulate immune pathways involved in HIV-1 infection.
- Sex differences impact disease manifestations in people living with HIV-1.

## Abstract

Immune responses are key in controlling viral infections such as HIV‐1, which remains a global challenge to public health. X/Y‐chromosome‐encoded genes and sex steroid hormones can modulate immune cells and drive distinct patterns of gene and protein expression involved in antiviral function, impacting sex‐dependent immune responses and altering the balance of specific immune pathways. These sex‐specific differences in antiviral immune responses have significant consequences for the outcome of HIV‐1 infection. A better understanding of sex differences in HIV‐1‐specific antiviral immunity is required to implement and develop new strategies for prevention, treatment and ultimately a functional cure against HIV‐1. Here we review the impact of X‐ and Y‐encoded genes and the role of sex steroid hormones on modulating antiviral immune responses against HIV‐1 and the consequences for disease manifestations in people living with HIV‐1.

## Full-text entities

- **Genes:** TBK1 (TANK binding kinase 1) [NCBI Gene 29110] {aka AIARV, FTDALS4, IIAE8, NAK, T2K}, IRF7 (interferon regulatory factor 7) [NCBI Gene 3665] {aka IMD39, IRF-7, IRF-7H, IRF7A, IRF7B, IRF7C}, FCGR3A (Fc gamma receptor IIIa) [NCBI Gene 2214] {aka CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA}, Nef [NCBI Gene 156110], CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, CD69 (CD69 molecule) [NCBI Gene 969] {aka AIM, BL-AC/P26, CLEC2C, EA1, GP32/28, MLR-3}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, MAVS (mitochondrial antiviral signaling protein) [NCBI Gene 57506] {aka CARDIF, IPS-1, IPS1, VISA}, DHX58 (DExH-box helicase 58) [NCBI Gene 79132] {aka D11LGP2, D11lgp2e, LGP2, RLR-3}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, gag-pol (Gag-Pol) [NCBI Gene 155348], FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, TLR8 (toll like receptor 8) [NCBI Gene 51311] {aka CD288, IMD98, TLR-8, hTLR8}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IRAK1 (interleukin 1 receptor associated kinase 1) [NCBI Gene 3654] {aka IRAK, pelle}, XIAP (X-linked inhibitor of apoptosis) [NCBI Gene 331] {aka API3, BIRC4, IAP-3, ILP1, MIHA, XLP2}, GPER1 (G protein-coupled estrogen receptor 1) [NCBI Gene 2852] {aka CEPR, CMKRL2, DRY12, FEG-1, GPCR-Br, GPER}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, DDX56 (DEAD-box helicase 56) [NCBI Gene 54606] {aka DDX21, DDX26, NOH61}, Vpu [NCBI Gene 155945], IRF5 (interferon regulatory factor 5) [NCBI Gene 3663] {aka SLEB10}, KLRC2 (killer cell lectin like receptor C2) [NCBI Gene 3822] {aka CD159c, NKG2-C, NKG2C}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], TAT (tyrosine aminotransferase) [NCBI Gene 6898], Rev. [NCBI Gene 155908], gag (Pr55(Gag)) [NCBI Gene 155030], RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925] {aka OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, KDM6A (lysine demethylase 6A) [NCBI Gene 7403] {aka KABUK2, UTX, bA386N14.2}, ESR2 (estrogen receptor 2) [NCBI Gene 2100] {aka ER-BETA, ESR-BETA, ESRB, ESTRB, Erb, NR3A2}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, NPTXR (neuronal pentraxin receptor) [NCBI Gene 23467] {aka NPR}, PRF1 (perforin 1) [NCBI Gene 5551] {aka HPLH2, P1, PFP}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CCR5 (C-C motif chemokine receptor 5) [NCBI Gene 1234] {aka CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5}, PRs [NCBI Gene 5640], TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, B3GAT1 (beta-1,3-glucuronyltransferase 1) [NCBI Gene 27087] {aka CD57, GLCATP, GLCUATP, HNK1, LEU7, NK-1}, CCR6 (C-C motif chemokine receptor 6) [NCBI Gene 1235] {aka BN-1, C-C CKR-6, CC-CKR-6, CCR-6, CD196, CKR-L3}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, RUNX1 (RUNX family transcription factor 1) [NCBI Gene 861] {aka AML1, AML1-EVI-1, AMLCR1, CBF2alpha, CBFA2, EVI-1}, PGRMC1 (progesterone receptor membrane component 1) [NCBI Gene 10857] {aka Dap1, HPR6.6, IZA, MPR}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, KDM5D (lysine demethylase 5D) [NCBI Gene 8284] {aka HY, HYA, JARID1D, SMCY}, RIEG2 (Rieger syndrome 2) [NCBI Gene 6012] {aka ARS, RGS2}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, UTY (ubiquitously transcribed tetratricopeptide repeat containing, Y-linked) [NCBI Gene 7404] {aka KDM6AL, KDM6C, UTY1}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, TASL (TLR adaptor interacting with endolysosomal SLC15A4) [NCBI Gene 80231] {aka CXorf21}, SHBG (sex hormone binding globulin) [NCBI Gene 6462] {aka ABP, SBP, TEBG}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, DDX3X (DEAD-box helicase 3 X-linked) [NCBI Gene 1654] {aka CAP-Rf, DBX, DDX14, DDX3, HLP2, MRX102}, S100A6 (S100 calcium binding protein A6) [NCBI Gene 6277] {aka 2A9, 5B10, CABP, CACY, PRA, S10A6}, SLC15A4 (solute carrier family 15 member 4) [NCBI Gene 121260] {aka FP12591, PHT1, PTR4}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}
- **Diseases:** infection (MESH:D007239), immune dysfunction (MESH:D007154), Leishmania mexicana infection (MESH:D007896), death (MESH:D003643), viral infections (MESH:D014777), chronic inflammation (MESH:D007249), systemic lupus erythematosus (MESH:D008180), IPEX (MESH:C580192), HIV (MESH:D015658), Immune dysregulation (OMIM:614878), hypogonadism (MESH:D007006), viremia (MESH:D014766), Loss of Y (OMIM:400043), AIDS (MESH:D000163), PLWH (MESH:C000719191), autoimmune disease (MESH:D001327)
- **Chemicals:** estriol (MESH:D004964), 27-hydroxycholesterol (MESH:C076996), 17-beta Estradiol (MESH:D004958), androstenedione (MESH:D000735), DHEA sulfate (MESH:D019314), growth hormones (MESH:D013006), uridine (MESH:D014529), DMPA (MESH:C050795), GAHAT (-), cholesterol (MESH:D002784), calcium (MESH:D002118), oligonucleotide (MESH:D009841), P4 (MESH:C015586), Progesterone (MESH:D011374), DHT (MESH:D013196), DHEA (MESH:D003687), testosterone (MESH:D013739), estrone (MESH:D004970), steroid (MESH:D013256), E4 (MESH:D004953)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Human immunodeficiency virus 1 (no rank) [taxon 11676]
- **Mutations:** rs179008

## Full text

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## References

200 references — full list in the complete paper: https://tomesphere.com/paper/PMC12921468/full.md

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Source: https://tomesphere.com/paper/PMC12921468