Retroviruses: Classification

Retrovirus

Introduction

Retroviruses are enveloped, positive-stranded, spherical RNA viruses showing a characteristic morphology and unusual mode of replication. The presence of an unusual enzyme—the RNA-dependent DNA polymerase or reverse transcriptase, giving the virus its name (retro meaning reverse)—is the unique feature of the viruses belonging to the family Retroviridae.

The enzyme reverse transcriptase prepares a DNA copy of the retroviral RNA genome—initially RNA–DNA hybrid and subsequently forms double-stranded DNA. The DNA copy of the viral genome is known as provirus. The provirus is then integrated into the host cell DNA to become a cellular gene for the rest of the life of the cell. This is in contrast to the classical transcription of the genetic information from DNA to RNA and then to proteins.

Baltimore and Tenin were the first to demonstrate that the retroviruses encode an RNA-dependent DNA polymerase and replicate through a DNA intermediate.

Retroviruses

Classification

All oncogenic RNA viruses are classified in the family Retroviridae; but all retroviruses are not oncogenic. The family Retroviridae, depending on (a) the diseases they cause, (b) tissue tropism and host range, (c) morphology of virions, and (d) genetic complexity are classified into three subfamilies, as follows:

Oncovirinae: The Oncovirinae or oncoviruses include onlythe retroviruses that can transform target cells. The viruses depending on their core and capsid, as demonstrated in electron microscopy, are classified further into types A, B, C, or D. These include human T-lymphotropic viruses (HTLV-1, HTLV-2, HTLV-3, and HTLV-4).

Lentivirinae: The lentivirinae or lentiviruses are slow (lent:slow) viruses associated with neurological and immunosup-pressive diseases in humans as well as in animals. These include human immunodeficiency viruses (HIV-1, HIV-2), Visna virus of sheep, and caprine arthritis/encephalitis virus of goat.

Spumavirinae: These consist of spumaviruses, which containnononcogenic “foamy viruses” (spuma: foam). These viruses are associated with asymptomatic infection in animals but are not associated with any human disease. Retroviruses belonging to these subfamilies associated with human diseases are summa-rized in Table 67-1.

The idea that cancer could be caused by a virus was first hypothesized by Peyton Rous (1911), when he transmitted solid tumors (sarcomas) of chicken by transplanting tissue. The belief that retroviruses could be associated with human leukemia was not in favor till discovery of bovine leukemia virus (BLV) and gibbon ape leukemia virus (GALV) in 1970s. This discovery led to increased interest in a potential human lymphotropic virus.

In 1960s, Tenin was the first to predict that retroviruses could replicate their RNA genome, by transcribing it into DNA by the enzyme reverse transcriptase. This observation was supported by results of a study reported separately by David Baltimore. The discovery of reverse transcriptase was revolu-tionary, because it contradicted the central dogma of molecular biology that genetic information is passed in one direction from DNA to RNA and then to protein. Baltimore and Tenin were awarded the Nobel Prize for their revolutionary work, which subsequently contributed immensely to the progress and developments in molecular biology.

Minna and Gazdar were the first to detect the first human leukemic retrovirus in 1979; but it was Poiesz and Gallo in 1980 who conclusively demonstrated the infectivity, antibody response, and evidence of provirus from the first human T-cell lymphotropic virus, or HTLV-1, isolated from a patient with a cutaneous T-cell malignancy. Subsequently, many human cancers caused by HTLV-1 were reported from different parts of the world.