Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model
IntroductionWhile HIV-1 subtype C (HIV-1C) is the most prevalent and widely distributed subtype in the HIV pandemic, nearly all current prevention and therapeutic strategies are based on work with the subtype B (HIV-1B). HIV-1C displays distinct genetic and pathogenic features from that of HIV-1B. T...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1552563/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850150442671013888 |
|---|---|
| author | Snehal Kaginkar Leila Remling-Mulder Ashashree Sahoo Tejaswini Pandey Pranay Gurav Jyoti Sutar Amit Kumar Singh Ella Barnett Sivasankar Panickan Ramesh Akkina Vainav Patel |
| author_facet | Snehal Kaginkar Leila Remling-Mulder Ashashree Sahoo Tejaswini Pandey Pranay Gurav Jyoti Sutar Amit Kumar Singh Ella Barnett Sivasankar Panickan Ramesh Akkina Vainav Patel |
| author_sort | Snehal Kaginkar |
| collection | DOAJ |
| description | IntroductionWhile HIV-1 subtype C (HIV-1C) is the most prevalent and widely distributed subtype in the HIV pandemic, nearly all current prevention and therapeutic strategies are based on work with the subtype B (HIV-1B). HIV-1C displays distinct genetic and pathogenic features from that of HIV-1B. Thus, treatment approaches developed for HIV-1B need to be suitably optimized for HIV-1C. A suitable animal model will help delineate comparative aspects of HIV-1C and HIV-1B infections.MethodsHere, we used a humanized mouse model to evaluate HIV-1C infection, disease progression, response to anti-retroviral therapy (ART) and viral rebound following therapy interruption. A limited comparative study with a prototypical subtype B virus was also performed. Viral infection, immune cell dynamics, acquisition of anti-retroviral therapy (ART) resistance and anatomical reservoir distribution following extended and interrupted therapy were compared. ResultsIn comparison, lower early plasma viremia was observed with HIV-1C, but with similar rate of CD4+ T cell depletion as that of HIV-1B. Viral suppression by ART was delayed in the HIV-1C infected group with evidence, in one case, of acquired class wide resistance to integrase inhibitors, a critical component of current global therapy regimens. Also, HIV-1C infected animals displayed faster rebound viremia following ART interruption (ATI). Disparate patterns of tissue proviral DNA distribution were observed following extended ART and ATI suggestive of distinct sources of viral rebound. DiscussionIn this preliminary study, discernible differences were noted between HIV-1C and B with implications for prevention, therapeutics and curative strategies. Results from here also highlight the utility of the hu-HSC mouse model for future expanded studies in this context. |
| format | Article |
| id | doaj-art-98224ac2e06e4373a2becf728daf4df8 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-98224ac2e06e4373a2becf728daf4df82025-08-20T02:26:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15525631552563Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse modelSnehal Kaginkar0Leila Remling-Mulder1Ashashree Sahoo2Tejaswini Pandey3Pranay Gurav4Jyoti Sutar5Amit Kumar Singh6Ella Barnett7Sivasankar Panickan8Ramesh Akkina9Vainav Patel10Viral Immunopathogenesis Laboratory, Indian Council of Medical Research (ICMR)- National Institute for Research in Reproductive and Child Health, Mumbai, IndiaDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesViral Immunopathogenesis Laboratory, Indian Council of Medical Research (ICMR)- National Institute for Research in Reproductive and Child Health, Mumbai, IndiaViral Immunopathogenesis Laboratory, Indian Council of Medical Research (ICMR)- National Institute for Research in Reproductive and Child Health, Mumbai, IndiaViral Immunopathogenesis Laboratory, Indian Council of Medical Research (ICMR)- National Institute for Research in Reproductive and Child Health, Mumbai, IndiaInternational AIDS Vaccine Initiative (IAVI)- Translational Health Science and Technology Institute (THSTI) Antibody Translational Research Program, Biotechnology Research and Innovation Council (BRIC)-Translational Health Science and Technology Institute, National Capital Region (NCR) Biotech Science Cluster, Faridabad, Haryana, IndiaViral Immunopathogenesis Laboratory, Indian Council of Medical Research (ICMR)- National Institute for Research in Reproductive and Child Health, Mumbai, IndiaDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesDepartment of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United StatesViral Immunopathogenesis Laboratory, Indian Council of Medical Research (ICMR)- National Institute for Research in Reproductive and Child Health, Mumbai, IndiaIntroductionWhile HIV-1 subtype C (HIV-1C) is the most prevalent and widely distributed subtype in the HIV pandemic, nearly all current prevention and therapeutic strategies are based on work with the subtype B (HIV-1B). HIV-1C displays distinct genetic and pathogenic features from that of HIV-1B. Thus, treatment approaches developed for HIV-1B need to be suitably optimized for HIV-1C. A suitable animal model will help delineate comparative aspects of HIV-1C and HIV-1B infections.MethodsHere, we used a humanized mouse model to evaluate HIV-1C infection, disease progression, response to anti-retroviral therapy (ART) and viral rebound following therapy interruption. A limited comparative study with a prototypical subtype B virus was also performed. Viral infection, immune cell dynamics, acquisition of anti-retroviral therapy (ART) resistance and anatomical reservoir distribution following extended and interrupted therapy were compared. ResultsIn comparison, lower early plasma viremia was observed with HIV-1C, but with similar rate of CD4+ T cell depletion as that of HIV-1B. Viral suppression by ART was delayed in the HIV-1C infected group with evidence, in one case, of acquired class wide resistance to integrase inhibitors, a critical component of current global therapy regimens. Also, HIV-1C infected animals displayed faster rebound viremia following ART interruption (ATI). Disparate patterns of tissue proviral DNA distribution were observed following extended ART and ATI suggestive of distinct sources of viral rebound. DiscussionIn this preliminary study, discernible differences were noted between HIV-1C and B with implications for prevention, therapeutics and curative strategies. Results from here also highlight the utility of the hu-HSC mouse model for future expanded studies in this context.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1552563/fullhumanized mice for HIV-1CHIV subtype C infection dynamics in humanized miceanti-retroviral therapy for HIV-1Cdrug resistance mutationsHIV-1C tissue reservoirtreatment interruption |
| spellingShingle | Snehal Kaginkar Leila Remling-Mulder Ashashree Sahoo Tejaswini Pandey Pranay Gurav Jyoti Sutar Amit Kumar Singh Ella Barnett Sivasankar Panickan Ramesh Akkina Vainav Patel Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model Frontiers in Immunology humanized mice for HIV-1C HIV subtype C infection dynamics in humanized mice anti-retroviral therapy for HIV-1C drug resistance mutations HIV-1C tissue reservoir treatment interruption |
| title | Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model |
| title_full | Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model |
| title_fullStr | Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model |
| title_full_unstemmed | Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model |
| title_short | Assessing HIV-1 subtype C infection dynamics, therapeutic responses and reservoir distribution using a humanized mouse model |
| title_sort | assessing hiv 1 subtype c infection dynamics therapeutic responses and reservoir distribution using a humanized mouse model |
| topic | humanized mice for HIV-1C HIV subtype C infection dynamics in humanized mice anti-retroviral therapy for HIV-1C drug resistance mutations HIV-1C tissue reservoir treatment interruption |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1552563/full |
| work_keys_str_mv | AT snehalkaginkar assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT leilaremlingmulder assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT ashashreesahoo assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT tejaswinipandey assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT pranaygurav assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT jyotisutar assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT amitkumarsingh assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT ellabarnett assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT sivasankarpanickan assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT rameshakkina assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel AT vainavpatel assessinghiv1subtypecinfectiondynamicstherapeuticresponsesandreservoirdistributionusingahumanizedmousemodel |