Send response to journal:
Re: Re: A simple request from the Perth Group

Lentiviruses are easily differentiated from other retroviruses both at the morphological level (the lentiviruses emerge from the cell as spheres and develop an electron dense cone shaped core as they mature: see this review by Gelderblom for an overview) and at the molecular level (lentiviruses all contain a number of regulatory genes such as tat, rev, nef and vif, and regulatory elements such as the RRE where the Rev regulatory protein binds and the TAR element where the Tat regulatory protein binds) which allow anyone to determine if the viruses produced by a transfection are endogenous viruses (such as HERV-K) or truly lentiviruses.

More importantly than just using molecular clones to observe viral morphology (as Bess, Gelderblom and hundereds of others have done), the Perth group is surely aware that molecular clones have also been used to tease apart the individual regions of the HIV and SIV genomes that contribute to pathology. For example, Rhesus macaques have been infected with molecular clones (and/or virus particles produced in cell culture from those clones) that are identical in genomic sequence other than a few specific point mutations. The great difference in pathogenicity between two nearly identical viral clones, indicates that these few sites that differ between the two are indeed contributing greatly to the pathogenicity of the virus. See for example:

Marthas ML, Ramos RA, Lohman BL, Van Rompay KK, Unger RE, Miller CJ, Banapour B, Pedersen NC, Luciw PA.
Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac.
J Virol. 1993 Oct;67(10):6047-55.
PMID: 8371353

Dehghani H, Brown CR, Plishka R, Buckler-White A, Hirsch VM.
The ITAM in Nef influences acute pathogenesis of AIDS-inducing simian immunodeficiency viruses SIVsm and SIVagm without altering kinetics or extent of viremia.
J Virol. 2002 May;76(9):4379-89.
PMID: 11932405

Hirsch VM, Sharkey ME, Brown CR, Brichacek B, Goldstein S, Wakefield J, Byrum R, Elkins WR, Hahn BH, Lifson JD, Stevenson M.
Vpx is required for dissemination and pathogenesis of SIV(SM) PBj: evidence of macrophage-dependent viral amplification.
Nat Med. 1998 Dec;4(12):1401-8.
PMID: 9846578

"...In other words, the transfection, if any, was of nucleic acids for which there is no proof they were either of HIV or any other retrovirus. ..."

Electron microscopy can only show us the general morphology of a virus. EIAV, FIV, BIV and SIV all look identical via electron micrography. FIV, BIV, and EIAV are totally harmless to humans, only HIV-1 and HIV-2 are known to cause immune deficiency in humans. The complete genome sequences of these viruses or their molecular clones, on the other hand, tells us EXACTLY which virus is present. The researchers who create infectious molecular clones of HIVs, SIVs, SHIVs (SIV-HIV chimeric viral genomes) and other viruses sequence the genomes before and after mutagenesis and before and after infections of animals. This is indeed far better proof that these viruses are viruses, than any electron micrograph could ever provide.

Competing interests:   None declared