{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T09:47:23Z","timestamp":1771667243385,"version":"3.50.1"},"reference-count":95,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FDA internal funding"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human immunodeficiency virus (HIV) type 2 (HIV-2) is less pathogenic than HIV-1. However, the factors responsible for the differences in pathogenicity are still not well defined. To investigate this issue, we performed infection of primary human monocyte-derived macrophages (MDMs) with individual HIV-1 or HIV-2 strains and compared the levels of M-CSF, a cytokine shown to promote HIV-1 infection and replication in our previous studies, and CXCL7, a chemokine identified as being expressed at levels correlated with HIV type by our preliminary gene-expression analysis. We tested several HIV-2 isolates able to replicate in human MDMs and observed that all of them induced the production of M-CSF at high levels similar to those previously established for HIV-1 infection. In addition, the production of M-CSF in MDMs infected with HIV-1 or HIV-2 isolates correlated with the extent of virus replication. In contrast to M-CSF, the chemokine CXCL7 was differentially expressed between MDMs infected with HIV-1 or HIV-2 isolates, as revealed by qPCR and ELISA testing. Together, these results suggest that M-CSF induction may play similar roles in promoting the replication of HIV-1 and HIV-2, while differential regulation of chemokine expression may be an important factor contributing to the differential pathogenicity of the two HIV subtypes.<\/jats:p>","DOI":"10.3390\/ijms26115028","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T06:35:09Z","timestamp":1747982109000},"page":"5028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage-Derived Factors with the Potential to Contribute to the Pathogenicity of HIV-1 and HIV-2: Roles of M-CSF and CXCL7"],"prefix":"10.3390","volume":"26","author":[{"given":"Chunling","family":"Gao","sequence":"first","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Kutza","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9978-3743","authenticated-orcid":false,"given":"Weiming","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Three (DPQR-III), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias A.","family":"Grimm","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Fields","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla S. R.","family":"Lankford","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franziska","family":"Schwartzkopff","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Paciga","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Machuca","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, Division of Emerging and Transfusion Transmitted Diseases (DETTD), Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Tiffany","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzanko","family":"Stantchev","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen A.","family":"Clouse","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Quality Research Four (DPQR-IV), Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.2174\/0929867023368935","article-title":"The role of monocytes and macrophages in the pathogenesis of HIV-1 infection","volume":"9","author":"Kedzierska","year":"2002","journal-title":"Curr. 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