Estudo da participação das proteínas Paxilina e Miosina-va na infectividade do Vírus Linfotrópico de Células T Humanas do tipo 1 (HTLV-1) / Study participation of Paxillin proteins and myosin-va in infectivity of the virus lymphotropic Human T cells type 1 (HTLV-1)

As ORFs I e IV do genoma do HTLV-1 codificam, respectivamente, as proteínas p12/p8 (acessória) e Tax (regulatória). p12/p8, de 99 aminoácidos, pode ser clivada em sua extremidade amino terminal gerando a proteína p8. A primeira clivagem proteolítica de p12 remove o sinal de retenção ao RE, enquanto a segunda clivagem, gera o produto de 8kDa, referido como p8. p12 localiza-se no sistema de endomembranes, residindo em RE e aparato de Golgi, enquanto p8 dirige-se para a membrana plasmática, onde é recrutada para a sinapse imunológica, através da ligação com o receptor de células T (TCR), além de participar da sinapse virológica e da formação de conduítes. A proteína Tax, por outro lado, atua como transativador transcricional do HTLV-1, sendo referida também na indução da expressão de diversos genes celulares, aumentando a proliferação e a migração das células infectadas. Na via de transporte de vesículas secretórias, vesículas produzidas como pós-Golgi são transportadas ao longo do citoesqueleto por motores celulares. A Miosina-Va, um motor não convencional, transporta diversos cargos, incluindo vesículas secretórias, vesículas sinápticas e de retículo endoplasmático. Outra proteína relacionada ao citoesqueleto é a Paxilina, que atua como molécula adaptadora nas adesões focais e cuja expressão está aumentada em indivíduos TSP-HAM...

HTLV-1 ORFs I and IV encode respectively p12/p8 (accessory protein) and Tax (regulatory protein). The 99 amino acid p12 protein can be proteolytically cleaved at the amino terminus to generate the p8 protein. The first proteolytic cleavage removes the ER retention/retrieval signal at the amino terminus of p12, while the second cleavage generates the p8 protein. The p12 protein localizes to cellular endomembranes, within the ER and Golgi apparatus, while p8 traffics to lipid rafts at the cell surface and is recruited to the immunological synapse upon T-cell receptor (TCR) ligation, virological synapse and conduits. Tax on the other hand acts as viral transactivator and induces expression of many cellular genes, increasing proliferation and migration of infected cells. In secretory vesicle transport, vesicles produced as post-Golgi are moved along the cytoskeleton by motor proteins. The unconventional myosin motor, Myosin-Va, moves several cargoes including secretory vesicles, synaptic vesicles, and the endoplasmic reticulum. Another cytoskeleton associated protein is Paxillin, an adapter on focal adhesions which expression is increased in TSP-HAM patients...

Proteína Tax ( HTLV-I ), probable factor patogénico y marcador del síndrome sicca que se asocia a HAM/TSP / Viral Tax protein expression in salivary glands of patients infected with human t-cell lymphotropic virus type I and Sicca Syndrome

Background: Human T-cell lymphotropic virus type I (HTLV-I) is a retrovirus that influences cellular metabolism modifying biological responses. This results in oncogenic, degenerative or inflammatory changes. The myelopathy associated to HTLV-I or tropical spastic paraparesia (HAM/TSP) is a mainly degenerative response to the virus infection. On the other hand, Sjögren syndrome has an inflammatory appearance. The immunohistochemical study of CD-4, CD-8 and CD45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein in pathological samples of salivary glands may help to differentiate primary from viral Sicca syndrome. Aim: To perform an immunohistochemical study of salivary glands of patients with HAM/TSP and Sicca syndrome and control subjects. Material and Methods: Pathological samples of salivary glands from 53 patients with HAM/TSP and Sicca syndrome and 10 control subjects, were studied. Immunohistochemistry was performed using antibodies against CD-4, CD-8 and CD-45 lymphocytes, metalloproteinase MMP-9 and viral Tax protein. Results: Only in patients with HAM/TSP and Sicca syndrome, the presence of Tax protein was observed in CD-4 and CD-8 lymphocytes and in glandular acini. Conclusions: Patients infected with HTLV-I express Tax protein in salivary glands. This finding has diagnostic and pathogenic implications.

Detection of px gene product of bovine leukemia virus in infected cells.

Bovine leukemia virus (BLV), like its closest relatives human T-cell leukemia virus-I and II, contain a 'px' gene, between the 'env' gene and the 3' long terminal repeat in its genome. A monoclonal antibody prepared against a synthetic oligopeptide whose sequence was deduced from highly conserved region of 'px' gene of BLV, was used to detect the presence of 'px' gene product in chronically BLV infected synchronised cells. By immunoperoxidase staining the 'px' gene product was detected maximum after 6-9 hr after synchronization in the nucleus of the cells which demonstrated the close interaction of it with viral DNA which is integrated with host cell genome.