Introduction:
Retroviruses are enveloped viruses containing two copies of single-stranded positive sense RNA. These viruses belong to a unique family of viruses, the Retroviridae, since their life cycle includes the special step of reverse transcription of their genomic RNA (gRNA) into DNA, which is then imported into the nucleus where it integrates into the host chromosomes.
Retroviruses infect a large number of host species and cause a variety of diseases, including immunodeficiency, tumors, and leukemia, both in humans and animals.
The retroviral replication cycle includes a cascade of events which are categorized into nine main steps in this review. They are: 1) attachment, membrane fusion and entry, 2) reverse transcription, 3) nuclear import and uncoating, 4) integration, 5) transcription and processing of viral RNAs, 6) their nuclear export, 7) protein synthesis, 8) gRNA packaging and virion assembly, 9) and finally virion release and maturation.
Expression of viral RNAs from the integrated provirus is facilitated by host enzymes. The U3 region contains a promoter for RNA polymerase II and other regulatory elements. The newly transcribed retroviral mRNAs and the genomic RNA resemble eukaryotic mRNAs and are 7-methyl guanosine capped at the 50 end and polyadenylated at the 30 end. However, unlike eukaryotic mRNAs that normally encode one protein, retroviral full-lengh RNA gives rise to multiple proteins from a single mRNA using two different mechanisms (translational read-through and ribosomal frameshift mechanisms). Additionally, they increase their coding capacity by generating subgenomic RNAs from canonical and alternate splicing. Both unspliced and spliced RNAs in retroviruses must be exported out of the nucleus into the cytoplasm, unlike the cellular RNAs where only the spliced RNAs are transported out of the nucleus.
Structure:
All known retroviruses encode four canonical proteins which are necessary for viral particle formation and its replication: Gag, protease (PR or Pro), polymerase (Pol) and envelope (Env). Based on their genomic complexity, retroviruses are classified into either simple or complex: simple retroviruses encode only gag, pro, pol and env genes (such as ALV and MLV), while complex retroviruses (such as HIV, HTLV, and MMTV) also encode a number of small regulatory and accessory proteins which are encoded from singly or alternatively spliced mRNAs.
Oncoviruses:
The first identified retrovirus was the causative agent of leukemia in chickens (avian leukosis virus; ALV) by Ellermann and Bang in 1908. The first and only known human retrovirus that causes malignancy, Human Tlymphotropic virus type 1 (HTLV-1), was discovered and described in 1980. Three years later, Montagnier and co-workers isolated a virus from the lymph nodes of patients with acquired immunodeficiency syndrome (AIDS) and in 1984, the link between HIV-1 and AIDS was established by Gallo and colleagues.
Human T cell lymphotropic (leukemia) viruses I (HTLV-I): was discovered some 6-7 years before HIV and is associated with adult T cell leukemia and HTLV-1 associated myelopathy. It is endemic to southwestern Japan, Carribean, Africa.
HTLV-1 has a C like nuclear capsid. Structurally it is similar to HIV. Its envelope is smaller. IMethods of transmission are the same as with HIV (with transmission during breast feeding thought to be important for pathogenesis).
HIV-1 may be a co-factor in accelerating progression to AIDS. In addition, other inflammatory disorders are potentially associated with HTLV-1 infection including Sjogrens syndrome (automimmune destruction of the salivary glands), arthritis, dermatitis and non-Hodgkins lymphoma.
HTLV-II: shares almost 50% overall homology with HTLV-1. It has no strong association with human disease and a high incidence of infection among IV users.
Lentiviruses:
Lentiviruses infect many different mammalian species. Infection with lentiviruses go through 3 stages; (1) an initial (acute) stage associated with rapid viral replication which is often accompanied by a transient period of disease, (2) a latent period during which the virus is brought under some immune control and no disease occurs and (3) high levels of viral replication later followed by disease.
All lentiviruses also persist for life and have high mutation rates. Lentiviruses replicate in the nucleus. Virus assembly is in the cytoplasm.
Feline immunodeficiency virus (FIV) is an enveloped, RNA virus that belongs to the Lentivirus genus of the Retroviridae. It infects domestic and wild cats worldwide, as well as hyenas. Like HIV, FIV establishes a chronic, persistent infection that, in some cats, ultimately culminates in immunodeficiency. Because of its similarities to HIV, FIV infection in cats has been used as a research model for HIV infection and acquired immunodeficiency syndrome (AIDS).
Like other retroviruses, FIV has a three-layered structure that is composed of an innermost genome-nucleocapsid complex with helical symmetry, an icosahedral capsid, and an envelope with glycoprotein spikes. The FIV genome contains three major genes: gag, which encodes the virion core proteins (capsid [p24], nucleocapsid, and matrix); pol, which encodes the reverse transcriptase, protease and integrase enzymes; and env, which encodes surface (gp120) and transmembrane virion (gp41) envelope glycoproteins.
HIV II:
Simian immunodeficiency virus (SIV): SIV is a model for human HIV infection.
Spumaviruses: include the foamy viruses.