| Title: |
Unique genetic signatures in HIV-1 subtype A1 and A1D recombinant envelope glycoprotein distinguish contemporary transmitted/founder viruses from historical strains in East Africa. |
| Authors: |
Kato, Frank; Kapaata, Anne; Galiwango, Ronald; Nakyanzi, Angella; Ndekezi, Christian; Natwijuka, Fortunate; Omara, Denis; Obuku, Andrew Ekii; Foley, Brian; Kaleebu, Pontiano; Nduati, Eunice; Balinda, Sheila Nina |
| Publisher Information: |
Frontiers Media |
| Publication Year: |
2025 |
| Collection: |
London School of Hygiene & Tropical Medicine: LSHTM Research Online |
| Description: |
INTRODUCTION: The envelope glycoprotein (Env) of HIV-1 Transmitted/Founder (T/F) viruses in subtypes B and C carries distinct genetic signatures that enhance transmission fitness, augment infectivity and immune evasion. However, there is limited data on such signatures in T/F subtypes A1, D and A1D recombinants that predominate East Africa's HIV epidemic. METHODS: We used phylogenetically corrected approaches to detect distinct genetic signatures by comparing 44 contemporary HIV-1 T/F Envs with 229 historical Envs of the same subtype in East Africa. RESULTS AND DISCUSSION: Subtype analysis based on the full-length Env gene of contemporary T/F viruses revealed a high proportion of subtype A1, followed by A1D recombinants, and fewer subtype D. Signature analysis revealed that the contemporary subtype A1 T/Fs were more likely to select distinct amino acids, including M22 in the signal peptide, R82 in gp120, A172 in the V2 loop, E230 in the glycosite 230, K275 in the D loop, Y317 in the V3 loop, K476 and N477 in the CD4 contact site, when compared with the historical Envs (q-value < 0.2). Conversely, the contemporary subtype A1 T/F Envs were less likely to carry the amino acids Q432 in the CD4 contact site, and the L784 signature within the LLP-2 (q-value < 0.2). The A1D recombinant T/Fs were more likely to select the D620 in the C-helix, but under selected the L34 in gp120, P299 in the V3 loop and Y643 in the Heptad repeat-2, compared to the historical Envs (q-value < 0.2). The distinct signature sites reported in this study may contribute to the successful establishment of acute infection as well as the persistence of long-term infection. Therefore, effective therapeutics and vaccines may target these distinct amino acid signatures especially for the East African region as it may be necessary to employ subtype-specific vaccines according to the subtype distribution. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text; application/pdf |
| Language: |
English |
| ISSN: |
1664-302X |
| Relation: |
https://researchonline.lshtm.ac.uk/id/eprint/4677365/1/Kato-etal-2025-Unique-genetic-signatures.pdf; https://researchonline.lshtm.ac.uk/id/eprint/4677365/7/fmicb-16-1632581.pdf; Kato, Frank ; Kapaata, Anne; Galiwango, Ronald; Nakyanzi, Angella; Ndekezi, Christian; Natwijuka, Fortunate; Omara, Denis; Obuku, Andrew Ekii; Foley, Brian; Kaleebu, Pontiano ORCID logo; +2 more.Nduati, Eunice; and Balinda, Sheila Nina (2025) Unique genetic signatures in HIV-1 subtype A1 and A1D recombinant envelope glycoprotein distinguish contemporary transmitted/founder viruses from historical strains in East Africa. Frontiers in microbiology, 16. 1632581-. ISSN 1664-302X DOI:10.3389/fmicb.2025.1632581 |
| DOI: |
10.3389/fmicb.2025.1632581 |
| Availability: |
https://researchonline.lshtm.ac.uk/id/eprint/4677365/; https://doi.org/10.3389/fmicb.2025.1632581 |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.F06C665D |
| Database: |
BASE |