Retrovirus

Retrovirus and cancer

The retroviruses fall into the list of pathogens potentially involved in the triggering of neoplastic forms: these viruses have gained a prestigious role in the research on cancer genetics in humans. For many years now, retroviruses have been at the center of scientific attention, as many of them are considered full-fledged oncogenic viruses. Furthermore, they can be exploited to introduce genes into mammalian cells, reprogramming their activity for therapeutic purposes (gene therapy, then inserting good genes into the cell) or technological (useful protein synthesis).

Entering a host cell, the retroviruses are able to convert their own genome from RNA to DNA: using the aid of the enzyme reverse transcriptase, the virus operates the so-called retro-transcription transforming the viral RNA into DNA. The latter is integrated into the DNA of the host cell which is exploited for genome synthesis and viral structures.

Retrovirus classification

The Retroviruses belong to as many as 5 viral families, among which that of the Retroviridae is the best known.

BASED ON PATHOGENICITY ?, the viruses belonging to the Retroviridae family are classified into three sub- families:

1. Oncovirus: they cause damage both in vitro and in vivo. Generally, retroviruses of this category are involved in the etiopathogenesis of tumor forms.
2. Spumavirus: although they are responsible for cytopathic effects in vitro (set of morphological alterations assumed by the virus-infected cell), their pathogenicity has not yet been demonstrated in vivo. Some authors insert the retrovirus HFV (hepatitis F virus) in this subfamily.
3. Lentiviruses: these retroviruses induce progressive impairment of the immune and neuronal systems.

The pathogenic retroviruses for humans are:

1. HIV or human immunodeficiency virus ( Human Immunodeficiency Virus ), belonging to the Lentivirus subfamily. Two serotypes have been identified in this category: HIV-1 and HIV-2. HIV is the causative agent of AIDS.
2. HTLV or Human T Lymphotropic virus : it belongs to the Oncovirus subfamily. Two serotypes were identified in this category: HTLV-1 and HTLV-2. The retroviruses belonging to this group are involved in the triggering of extremely serious pathologies, such as acute T-cell leukemia, hairy cell leukemia and myelopathies (diseases affecting the spinal cord).

ON THE BASIS OF THE GENOME AND THE REPRODUCTIVE CYCLE, the retroviruses are divided into two macro-groups, respectively called "group VI" and "group VII":

1. Single-stranded RNA retrovirus (group VI): the HIV virus is the exponent of this category. After entering the host cell, the retrovirus genome undergoes retro-transcription and is converted into DNA by the reverse transcriptase enzyme. The replication of these retroviruses occurs in the cytoplasm of the infected cell. Subsequently the retrovirus, infecting the nucleus, integrates with the genome of the host cell (by the integrase enzyme): the virus can remain silent for variable periods of time. At this point, double-stranded DNA is exploited for transcription of messenger RNA (mRNA), from which - at the ribosomal level - viral proteins are synthesized. The newly formed virions escape from the cell and are free to infect neighboring cells, spreading like wildfire.

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2. DNA double-stranded retrovirus (group VII): this category includes the hepatitis B virus. These retroviruses have a double-stranded DNA genome: once inside the target cell, the virus proceeds from the cytoplasm to the nucleus. Having arrived here, the virus genome mixes with that of the host cell and is replicated: the "new" DNA serves to produce mRNA, which in turn produces viral proteins. Pre-genomic RNA will be transformed into DNA through a reverse transcription (performed by viral enzymes newly synthesized), which is incorporated into other neosynthesised viral structures: at this point, the replication cycle is terminated.

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There is another category of retroviruses, called endogenous : these viruses are integrated with the genome of the host cell, and are genetically transmitted. In other words, endogenous retroviruses are able to infect germ cells, therefore they can be transmitted vertically through the germ line.

General characteristics

The Retrovirus virion has a rough-spherical shape, with a diameter ranging from 100 to 120 nm. The Retroviruses belonging to the Retroviridae family (the best known) have a genome consisting of two single-stranded RNA molecules, with positive polarity.

Although numerous, retroviruses are quite similar to each other:

• All Retroviruses have an external lipoprotein membrane called pericapside or envelope
• The enzyme reverse transcriptase is indispensable for transforming the genome from RNA into DNA
• The genome of retroviruses contains at least three genes essential for virus replication:
  • GAG ( group specific antigen ), whose function is to code for structural proteins. GAGs are the main components of the viral capsid (2, 000-4, 000 copies per virion).
  • POL (stands for polymerase ), whose function is to code for the enzymes reverse transcriptase, proteases and integrases, useful for virus replication.
  • ENV (diminutive of envelope ), whose function is to code for membrane proteins (pericapside).
  Upstream and downstream of these genes we find two LTR sequences, acronym of Long Terminal Repeat, (located at 5 'and 3' of the proviral genome): these sequences act as promoters and polyadenylation signals, given that they contain some regions involved in reverse transcription, integration and control of viral genome expression.
• In addition to the genes just described, the genome of retroviruses contains further genes called accessories, which are essential for increasing the virulence and pathogenicity of the retrovirus.