Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

Münch, J. et al. Cell. 131, 1059-1071 (2007)

Speaker: Shi-Yu Chao                                            Time: 14:00~15:00, Apr. 15, 2009

Commentator: Dr. Shainn-Wei Wang                      Place: Room 601

Abstract:

        Over the past 25 years, HIV has infected about 33 million people and caused 2 million death in 2007 (UNAIDS). Although the HIV continues to spread world-wide, the retrovirus is a surprisingly weak pathogen in term of its overall infectivity. The ratio of detectable infectious units to virus particles is on the order of 1:1,000 to 1:100,000 in vitro. More than 80% HIV transmission is acquired through heterosexual contact, most frequently by women through vaginal intercourse[1]. A hypothesis is that semen contains one or more factors that can modulate HIV infectivity, but it is stillpoorly understood. In this study, the authors identified a factor from a semen fluid derived peptide/protein library that could enhance the infection of HIV-1. The enhancing factor is a fragment of prostatic acid phosphatase (PAP), corresponding to amino acid 248 to 286 by mass spectrometry and peptide sequencing. To exclude the possibility of contamination, they employed chemically synthesized PAP peptide (PAP248-286) to study its infection enhancement. They found that the PAP248-286 would spontaneously form amyloid fibrils in solution during storage or agitation, and these fibrils strongly enhanced the infection of HIV-1 directly and in trans. The authors named these fibrils semen-derived enhancer of viral infection (SEVI). The HIV-1 infectivity enhancement of SEVI is viral geno- and pheno-type independent, and also cell type independent. In 2009, the cooperativeresearch group characterized cationic properties of SEVI and underlied its ability to enhance HIV-1 infection[2]. SEVI efficiently bind to virions and cell surfaces that promote physical interaction between virions and target cells, but the entry of HIV-1 still requires for CD4 and coreceptors. Taken together, these findings suggest that amyloidogenic PAP fragments, which are abundant in seminal fluid and can enhance virus-host interaction, may play an important role in sexual transmission of HIV.

References:

1. Haase, A.T. (2005) Perils at mucosal front lines for HIV and SIV and their hosts. Nat. Rev. Immuno. 5, 783-792.

2. Roan, N.R. et al. (2009) The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection. J. Virol. 83, 73-80.