The Contributions of the Gallo Team and the Montagnier Team to the Discovery of the AIDS Virus

In this paper I review the main works of the teams headed by Robert Gallo and Luc Montagnier which led to the discovery of the HIV retrovirus and to the blood test with which one can prove HIV infection. I show that this discovery which saved millions of human lifes (and perhaps the survival of mankind) was made possible only (i) because Gallo's team discovered the T-cell lymphocyte growth factor with which they were able to discover the first retrovirus that infects humans (HTLV-I) and their hypothesis that AIDS is caused by a retrovirus, and (ii) because Montagnier's team detected an antibody against alpha interferon in order to enhance retrovirus production with which they were able to discover the HIV retrovirus and their examination and blood test that gave evidence that HIV causes AIDS. Their examination was improved by the Gallo team who proved without doubt that HIV is the cause of AIDS. I leave the question open whether Gallo deserved the Nobel Prize or whether the Nobel committee's decision to award the prize only to Montagnier and Barre-Sinoussi was correct.

The Contributions of the Gallo Team and the Montagnier Team to the Discovery of the AIDS Virus

In this paper I review the main works of the teams headed by Robert Gallo and Luc Montagnier which led to the discovery of the HIV retrovirus and to the blood test with which one can prove HIV infection. I show that this discovery which saved millions of human lifes (and perhaps the survival of mankind) was made possible only (i) because Gallo's team discovered the T-cell lymphocyte growth factor with which they were able to discover the first retrovirus that infects humans (HTLV-I) and their hypothesis that AIDS is caused by a retrovirus, and (ii) because Montagnier's team detected an antibody against alpha interferon in order to enhance retrovirus production with which they were able to discover the HIV retrovirus and their examination and blood test that gave evidence that HIV causes AIDS. Their examination was improved by the Gallo team who proved without doubt that HIV is the cause of AIDS. I leave the question open whether Gallo deserved the Nobel Prize or whether the Nobel committee's decision to award the prize only to Montagnier and Barre-Sinoussi was correct.

Critical Role of Epstein-Barr Virus (EBV)-Encoded RNA in Efficient EBV-Induced B-Lymphocyte Growth Transformation

ABSTRACT It was demonstrated that Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) were nonessential for B-lymphocyte growth transformation. We revisited this issue by producing a large quantity of EBER-deleted EBV by using an Akata cell system. Although the EBER-deleted virus efficiently infected B lymphocytes, its 50% transforming dose was approximately 100-fold less than that of the EBER-positive EBV. We then engineered the genome of EBER-deleted virus and generated a recombinant virus with the EBER genes reconstituted at their native locus. The resultant EBER-reconstituted EBV exhibited restored transforming ability. In addition, lymphoblastoid cell lines established with the EBER-deleted EBV grew significantly more slowly than those established with wild-type or EBER-reconstituted EBV, and the difference between the growth rates was especially highlighted when the cells were plated at low cell densities. These results clearly demonstrate that EBERs significantly contribute to the efficient growth transformation of B lymphocytes by enhancing the growth potential of transformed lymphocytes.

Janus Kinases Interact with and Phosphorylate Rack-1 (Receptor for Activated C Kinase-1), a WD Motif Containing Protein.

We recently reported that Tyk2 was essential for IFN-a-induced B lymphocyte growth inhibition, although Stat1 is not required for this IFN-a-mediated inhibition. This means that other signaling molecules besides Stat1, and which are activated by Tyk2, are thought to transduce the IFN-a signal inhibiting B lymphocyte growth. We performed a yeast two-hybrid screen for proteins that interact with Tyk2, and identified Rack-1, originally described as a receptor for activated C kinase beta, associated with Tyk2. Receptor for activated C kinase (Rack)-1 is a protein kinase C interacting protein, and contains a WD repeat but has no enzymatic activity. In addition to protein kinase C, Rack-1 also binds to Src, phospholipase C gamma, and ras-GTPase-activating proteins. Thus, Rack-1 is thought to function as a scaffold protein that recruits specific signaling elements. In a cytokine signaling cascade, Rack-1 has been reported to interact with the IFN-alpha/beta receptor and Stat1. In addition, we show here that Rack-1 associates with a member of Jak, tyrosine kinase 2 (Tyk2). Rack-1 interacts weakly with the kinase domain and interacts strongly with the pseudo-kinase domain of Tyk2. Rack-1 associates with Tyk2 via two regions, one in the N-terminus and one in the middle portion (a.a.138–203) of Rack-1. In addition, not only Tyk2 but other Jak kinases associate with Rack-1, and each Jak activation causes the phosphorylation of Tyrosine 194 on Rack-1. After phosphorylation, Rack-1 is translocated from cytoplasm or membrane toward the perinuclear region. In addition to functioning as a scaffolding protein, these results raise the possibility that Rack-1 functions as a signaling molecule in cytokine signaling cascades.