Human T-Lymphotropic Viruses: Properties of the Virus

Human T-Lymphotropic Viruses

HTLV-1 is one of the six distinct retroviruses known to infect human lymphocytes, others being HTLV-2, HTLV-3, HTLV-4, HIV-1, and HIV-2. HTLV and HIV are two important members of the retrovirus family. Both the viruses are the enveloped viruses. Both have enzyme reverse transcriptase in the virion and two copies of a single-stranded, positive-polarity RNA genome.

Properties of the Virus

◗ Morphology

HTLV-1 shows following features:

·           It is an enveloped, spherical virus measuring 100 nm in diameter.

·           The virus consists of a single-stranded RNA with diploid genome, which has the property to replicate through DNA intermediary and is able to integrate into host T cell genome as a provirus.

·           The genome contains LTRs, which encode for a large number of polyproteins processed by virally encoded protease and cellular protease into functional peptides. The gene px encodes for Tax and Rex proteins, which regulate gene expression in the virus. The gag gene encodes structural proteins of matrix, capsid, and nucleocapsid; pol gene encodes several enzymes, such as protease, polymerase, and integrase; env gene encodes gp46 and gp21 (a 221-kDa transmembrane glycoprotein).

·           HTLV is morphologically similar to HIV except that it has a centrally located nucleocapsid core in a mature virion. HTLV also differs from HIV by having a unique genome. The genome has the same gag–pol–env motif with LTR sequences as those of HIV, but it differs from HIV by having a fourth sequence (xp), which participates in transcription.

◗ Viral replication

The HTLV has two important genes tax and rex, which regulate viral replication. The main function of tax gene is transactiva-tion of viral and cellular genes, and that of rex gene is regulation of RNA splicing and promotion of export to cytoplasm.

Tax gene: It is a transcriptional activator, which enhances tran-scription of the viral genome from the promoter gene sequences in the LTR. It also activates other genes including those for interleukin (IL)-2, IL-3, GM-CSF (granulocyte macrophage colony-stimulating factor), and the receptor for IL-2. Activation of this gene promotes the growth of infected T cells.

Rex gene: It encodes two proteins that bind to structure on theviral mRNA and thereby prevent splicing and promote mRNA transport to the cytoplasm. Later during the course of infec-tion, the rex gene selectively enhances expression of the singly sliced structural genes, which are required in large quantities.

HTLV primarily infects CD41 cells. The virus enters the cell and within the cytoplasm, reverse transcriptase of the virion synthesizes a DNA copy of the genome. The genome is then transported into the nucleus and is integrated with the cell DNA by the virally encoded integrase, resulting in an infection. The host cell RNA polymerase makes viral RNA, and transcrip-tion is upregulated by Tax protein. The latter facilitates transcription of viral genome and Rex protein modulates processing of viral pre-mRNA.

The Rex protein controls the synthesis of the gag/pol mRNA, the env mRNA, and their subsequent transport to the cytoplasm, where they are translated into structural viral pro-teins. Virion genome RNA is also synthesized and transported to the cytoplasm. The virus-encoded protease mediates conver-sion of precursor polypeptides into functional structural proteins. The nucleocapsid of the virion is assembled in the cytoplasm and budding takes place at the outer cell membrane.

◗ Antigenic and genomic properties

Six different HTLV-1 subclasses exist. Each subtype is endemic in a particular geographical area. The oncoviruses include HTLV-1, HTLV-2, and HTLV-3, but only HTLV-1 has been associated with human disease. HTLV-1 and HTLV-2 share as much as 50% homology. Two new HTLVs, HTLV-3 and HTLV-4, have recently been described in a small number of Africans, with no particular illness.