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Simian-human immunodeficiency virus (SHIV) is a bioengineered virus that combines genes from the human immunodeficiency virus-1 (HIV-1) with genes from simian immunodeficiency virus (SIV), developed as a tool to investigate the infectiveness and pathology of HIV-1 in nonhuman primate model systems. 

Several distinct lineages of SIV are known, which infect more than 40 natural primate hosts.  As a result of the long co-evolution of these hosts and SIV strains, natural hosts show reduced or nonpathogenic response to SIV infection.  However SIV can also infect non-natural primate hosts, such as macaque monkeys, in which infection can develop into simian AIDS that has a course and pathology similar to AIDS in humans.  The rapid evolution and diversity of the HIV genome has posed significant difficulty for the design of an effective vaccination.  While macaques are clearly the best non-human primate model for HIV/AIDS research, SIV and HIV-1 are genetically distinct in enough ways that the macaque antigenic response to SIV does not always represent the human response to HIV-1. 

In the 1990s, scientists engineered the first transgenic simian-human virus (SHIV89.6P) to better mimic the effect of the human virus within the setting of nonhuman primate models where the infection and pathology can be studied.  Multiple other various SHIV isolates have since been engineered, most of them consisting of a SIV genetic backbone with the HIV forms of an important genes such as, for example, the HIV gene coding for the viral membrane (env).  SHIV isolates have been used to investigate the effects of drugs and vaccines upon particular, specific components of the human virus, and to identify host and viral factors involved in transmission and early immune response of macaques to inoculation.  One particular virus construct, SHIVSF33, adapted into a more pathogenic form over generations in macaque cells, allowing researchers to identify specific amino acid mutations in the env gene correlated with increased virulence.  Researchers can choose chimeras with different levels of pathogenicity, transmission abilities, and host specificities appropriate for their particular investigation.  To further narrow the distance between SHIV constructions and the HIV-1 virus, newer generation SHIVs have been engineered to include more than one HIV-1 gene in the SIV backbone, and has pushed SHIV/HIV-1 genomic identity to greater than 90%.  The hope with this research is to create infection that maximally mimics HIV-1 in animal models thereby simplifying analysis of clinical trials in humans.  Research is progressing to make these tools viable.  A great general overview of SHIVS and associated research written by Pereira, Srinivasan and Smith is available at http://www.intechopen.com/books/immunodeficiency/simian-human-immunodeficiency-viruses-and-their-impact-on-non-human-primate-models-for-aids.

(Barouch et al. 2013; Haigwood 2010; IAVI 2008; Pal et al. 2012; Pereira et al. 2010)

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