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Additionally, antiretroviral drugs have provided an effective means of protection against HIV transmission. Despite these advances, significant limitations exist; namely, the inability to eliminate HIV reservoirs, the inability to reverse lymphoid tissues damage, and the lack of an effective vaccine for preventing HIV transmission. Evaluation of the safety and efficacy of therapeutics and vaccines for eliminating HIV reservoirs and preventing HIV transmission requires robust in vivo models. Since HIV is a human-specific pathogen, that targets hematopoietic lineage cells and lymphoid tissues, in vivo animal models for HIV-host interactions require incorporation of human hematopoietic lineage cells and lymphoid tissues. In this review, we will discuss the construction of mouse models with human lymphoid tissues and\/or hematopoietic lineage cells, termed, human immune system (HIS)-humanized mice. These HIS-humanized mouse models can support the development of functional human innate and adaptive immune cells, along with primary (thymus) and secondary (spleen) lymphoid tissues. We will discuss applications of HIS-humanized mouse models in evaluating the safety and efficacy of therapeutics against HIV reservoirs and associated immunopathology, and delineate the human immune response elicited by candidate HIV vaccines. In addition to focusing on how these HIS-humanized mouse models have already furthered our understanding of HIV and contributed to HIV therapeutics development, we discuss how emerging HIS-humanized rat models could address the limitations of HIS-mouse models.<\/jats:p>","DOI":"10.1186\/s12977-020-00515-3","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T15:03:47Z","timestamp":1586531027000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies"],"prefix":"10.1186","volume":"17","author":[{"given":"Yash","family":"Agarwal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole","family":"Beatty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivkumar","family":"Biradar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Castronova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Melody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5153-2718","authenticated-orcid":false,"given":"Moses Turkle","family":"Bility","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,10]]},"reference":[{"issue":"7787","key":"515_CR1","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/s41586-019-1841-8","volume":"576","author":"T Ndung\u2019u","year":"2019","unstructured":"Ndung\u2019u T, McCune JM, Deeks SG. 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Written informed consent of the maternal donors was obtained in all cases, under IRB of the University of Pittsburgh guidelines and federal\/state regulations. The use of human fetal organs\/cells to construct humanized mice was reviewed by the University of Pittsburgh\u2019s IRB office, which has determined that this submission does not constitute human subject research as defined under federal regulations (45 CFR 46.102[d or f] and 21 CFR 56.102[c], [e], and [l]). The use of human hematopoietic stem cells was reviewed and approved by the Human Stem Cell Research Oversight (hSCRO) at the University of Pittsburgh. The use of biological agents (e.g., HIV), recombinant DNA, and transgenic animals was reviewed and approved by the Institutional Biosafety Committee (IBC) at the University of Pittsburgh. All animal studies were approved by the IACUC at the University of Pittsburgh and were conducted following NIH guidelines for housing and care of laboratory animals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8"}}