Cellular Localization Determinants of the HIV-2 Vpx Protein

Start Date

15-4-2021 2:00 PM

End Date

15-4-2021 3:00 PM

Student's Major

Biological Sciences

Student's College

Science, Engineering and Technology

Mentor's Name

Allison Land

Mentor's Department

Biological Sciences

Mentor's College

Science, Engineering and Technology

Description

Human immunodeficiency virus type 2 (HIV-2) is a lentivirus which is a type of retrovirus. Retroviruses insert their viral genome into the host genome by reverse transcription and can cause chronic or delayed disease. HIV-2 contains Viral protein x (Vpx), which is not encoded in human immunodeficiency virus type 1 ( HIV-1). Vpx interacts with human sterile alpha motif and HD-domain-containing protein 1 (SAMHD1), which breaks down lone nucleotides, thereby decreasing viral replication. Vpx counteracts the function of SAMHD1, leading to more nucleotides available for viral replication. Prior, unpublished research in Dr. Allison Land’s lab has noted a difference in the localization of Vpx from two different strains of HIV-2: HIV-2 ROD9 and HIV-2 7132a. After transfection into HeLa cells, HIV-2 7132a Vpx was mostly cytoplasmic, while HIV-2 ROD9 Vpx was present in the cytoplasm and the nucleus. Our research goal is to identify the cause of this difference in localization. We hypothesize that by mutating key amino acids in HIV-2 ROD9 Vpx to match HIV-2 7132a Vpx, HIV-2 ROD9 Vpx localization will shift from cell wide to primarily cytoplasmic (matching HIV-2 7132a Vpx localization). By comparing the amino acid sequence of Vpx from HIV-2 ROD9 and HIV-2 7132a, we identified sites of significant difference and mutated two of these sites causing the amino acids to change and match the other Vpx protein. Next, the mutated plasmids will be transfected into HeLa cells, and the expression of Vpx will be observed. By learning about the different regions in the Vpx sequence that affect localization, the infectious process of HIV-2 can be better understood which will allow for further research on how to treat this disease.

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Apr 15th, 2:00 PM Apr 15th, 3:00 PM

Cellular Localization Determinants of the HIV-2 Vpx Protein

Human immunodeficiency virus type 2 (HIV-2) is a lentivirus which is a type of retrovirus. Retroviruses insert their viral genome into the host genome by reverse transcription and can cause chronic or delayed disease. HIV-2 contains Viral protein x (Vpx), which is not encoded in human immunodeficiency virus type 1 ( HIV-1). Vpx interacts with human sterile alpha motif and HD-domain-containing protein 1 (SAMHD1), which breaks down lone nucleotides, thereby decreasing viral replication. Vpx counteracts the function of SAMHD1, leading to more nucleotides available for viral replication. Prior, unpublished research in Dr. Allison Land’s lab has noted a difference in the localization of Vpx from two different strains of HIV-2: HIV-2 ROD9 and HIV-2 7132a. After transfection into HeLa cells, HIV-2 7132a Vpx was mostly cytoplasmic, while HIV-2 ROD9 Vpx was present in the cytoplasm and the nucleus. Our research goal is to identify the cause of this difference in localization. We hypothesize that by mutating key amino acids in HIV-2 ROD9 Vpx to match HIV-2 7132a Vpx, HIV-2 ROD9 Vpx localization will shift from cell wide to primarily cytoplasmic (matching HIV-2 7132a Vpx localization). By comparing the amino acid sequence of Vpx from HIV-2 ROD9 and HIV-2 7132a, we identified sites of significant difference and mutated two of these sites causing the amino acids to change and match the other Vpx protein. Next, the mutated plasmids will be transfected into HeLa cells, and the expression of Vpx will be observed. By learning about the different regions in the Vpx sequence that affect localization, the infectious process of HIV-2 can be better understood which will allow for further research on how to treat this disease.