Gag-Gag Interactions Are Insufficient to Fully Stabilize and Order the Immature HIV Gag Lattice

Author:

Saha,Ipsita [ORCID]

Preece, Benjamin

Peterson, Abby

Durden, Haley

MacArthur, Brian

Lowe, Jake

Belnap, David

Vershinin, Michael

Saffarian, Saveez [ORCID]
Author Address

Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA., Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA., Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112, USA., School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA., Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA.,

Abstract:

Immature HIV virions harbor a lattice of Gag molecules with significant ordering in CA-NTD, CA-CTD and SP1 regions. This ordering plays a major role during HIV maturation. To test the condition in which the Gag lattice forms in vivo, we assembled virus like particles (VLPs) by expressing only HIV Gag in mammalian cells. Here we show that these VLPs incorporate a similar number of Gag molecules compared to immature HIV virions. However, within these VLPs, Gag molecules diffuse with a pseudo-diffusion rate of 10 nm2/s, this pseudo-diffusion is abrogated in the presence of melittin and is sensitive to mutations within the SP1 region. Using cryotomography, we show that unlike immature HIV virions, in the Gag lattice of VLPs the CA-CTD and SP1 regions are significantly less ordered. Our observations suggest that within immature HIV virions, other viral factors in addition to Gag, contribute to ordering in the CA-CTD and SP1 regions.

See More

Author Address