General Morphology

Mode of Transmission and Pathology

According to the literature⁶, SIV is transmitted sexually. Though it is safe to infer from the modes of transmission of HIV, BIV, and FIV, that transmission can be caused by any form of fluid transmission by biting, open wounds, nursing, etc. But rarely is SIV transmitted vertically. ⁴

Surprisingly, as observed in our day and age, SIV infections rarely progress into AIDS. Some scientists believe this is due to a "coadaptation" between primates and these retroviruses over long evolutionary time periods. This is supported by the higher incidence of AIDS in chimpanzees who are infected with an new strain of SIVcpz from preying on other monkeys.⁹ Despite their AIDS resistance, the onset of SIV can be detected by an acute infection phase which there is a large increase of macrophages, neutrophils, and dendritic cells paired with a slow loss of activated CD4+ T cells. Chronic infection afterwards is quite benign; T helper 17 and T helper 2 CD4+ cells are not depleted and levels of immune signalling ligands such as interferon alpha and beta eventually resolve.

Gene Therapy/Bioengineering Applications/Modfications of SIV

Interestingly a research group has merged the SIV and HIV viruses to form a chimeric SHIV virus. In 1992, Shibata and Adachi succesfully created a HIV-1/SIV chimera, called the NM-3 virus, which was found to infect in a macque, in hopes of finding a vaccine for HIV-1.¹ With that technology, more recently, a group transfected stem cell with a "937-bp antisense HIV-1 envelope sequence" to inhibit the replication of SIV/HIV-1 chimera viruses with HIV-1 envelopes in rhesus bone marrow cells.² And in 2003, Center et al. modified HIV Env by replacing some of its sequence with HIV-1/SIV chimera sequence in order to increase the trimerization for gp140 protein of HIV-1, implicitly in hopes of using this new virus to induce the creation better antibodies in a host for a possible HIV-1 vaccine.³

SIV and HIV

Due to the significant similarities between SIV and HIV and because SIV is evolutionary older⁴, AIDS has been considered by some scientists as a zoonosis; hence, at some point, SIV was transferred to a human. There are a number of theories but these zoonosis theories are not proven and are still questioned. One such zoonosis theory is the Hunter theory in which the blood of killed or eaten chimps enters the wounds of a hunter, and SIV by chance is able to adapt and develop into HIV. Other theories include the contaminated needle theory, the colonialism theory, and oral polio vaccine theory.⁵ In part, this is fodder for the flame of research to understanding SIV. Moreover, the macque AIDS phenotype looks very similar to the human AIDS phenotype, so efforts to cure SIV may have implications to an HIV cure.

There are numerous strains of SIV, which affect different species of primates. The earliest discovered strain was found in macques⁷; others discovered later include gorilla, chimpanzee, sooty mangabey, mandrilla, and more.^4,8 Likewise two strains of HIV: worldspread HIV-1 and predominately Western Africa HIV-2, are broken down into subgroups from A to K. This has led to work in SIV and HIV phylogeny and understanding the evolution of each strain of each virus, in hopes of finding the link between the two, and possibly the root of both viruses.

SIV-mnd2 and SIV-afm1 Homology

After performing a simple nucleotide blast blastn on BLAST, I was able to obtain a simple dotplot of the genome homogly between a SIV-mnd2 and SIV-afm1 as shown below.

From the image, we can see that the gag gene(~700 to ~2,200) and a significant portion of the pol gene (~2,700 to ~5000) are highly conserved with reoughly 69% homology for both sequences. Interestingly a really minor portion of the env gene (~6300 to ~8900) is conserved (~66% homolgy). This might be due to the fact that the env gene encodes the important glycoproteins that dictate the invasion of the virus. Highly adpative SIV can detect and mutate their genomes depending on the minor differences in the CD4 and CCR5 chemokine primate analog receptors of different primates species. SIV might find it favorable to alter its env genes to prevent detect from immune cells and/or protect itself against antibodies.

Multiple Sequence Alignment of Subset of Ribovira Genomes

To get a basic idea of the phylogeny of Retroviridae, Picornaviridae, Coronaviridae, Flaviviridae, and Paramyxoviridae, randomly selected representative genomes(SIV, human Rhinovirus 14, SARS, West Nile virus, and Mumps) were aligned by ClustalW. Interestingly SIV-mnd2 is the most genetically homolgous to the West Nile (type 1) virus at ~19.6%. SIV was roughly 18-19% homologous to the the remaining four viruses as well.

Viral Cell Cycle

Click the picture to watch the animation!
Image taken from www.brittanica.com

Other Resources

Viral Zone: Lentiviruses

Wikipedia: SIV

ICTVdB

Other viruses

References

1. Shibata, Riri and Adachi, Akio. SIV/HIV Recombinants and Their Use in Studying Biological Properties. AIDS Research and Human Retroviruses. Vol. 8, Number 3, 1992. Mary Ann Liebert, Inc., Publishers.

2. Braun,E Stephen. Inhibition of simian/human immunodeficiency virus replication in CD4+ T cells derived from lentiviral-transduced CD34+ hematopoietic cells. Molecular Therapy (2005) 12, 1157-1167; doi: 10.1016/j.ymthe.2005.07.698

3. Center, J. Rob et al. Promoting Trimerization of Soluble Human Immunodeficiency Virus Type 1 (HIV-1) Env through the Use of HIV-1/Simian Immunodeficiency Virus Chimeras. Journal of Virology. 2004 March; 78(5): 2265-2276. doi: 10.1128/JVI.78.5.2265-2276.2004.

4. Sodora L Donald, et al. Toward an AIDS vaccine: lessions from natural simian immunodeficiency virus infections of African nonhuman primate hosts. Nature Medicine 15 861-865 (2009). doi:10.1038/nm.2013

5. SIV: Theories about the Origin of HIV

6. Otsyula M, et al. Transmission of simiam immunodeficiency virus (SIV) in naturally infected African green monkeys (AGMs). J Med Primatol. 1992 Feb-May; 21:72

7. Wikipedia: SIV

8. Heuverswyn, Van Fran, et al. Human immunodeficiency viruses: SIV infection in wild gorillas. Nature 444, 164; Nov 2006. doi:10.1038/444164a 9. Sharp, P.M., Shaw, G.M. & Hahn, B.H. Simian immunodeficiency virus infection of chimpanzees. J. Virol. 79, 3891–3902 (2005).