Retroviruses

Retroviruses possess an enzyme, reverse transcriptase that can transcribe ssRNA into double-stranded DNA. This activity is reflected in the designation “retroviruses.” Integration of the DNA thus derived from the viral genome in the host-cell genome is a precondition for viral replication. Certain retro­viruses are also capable of oncogenic cell transformation. Due to this poten­tial and their RNA genome, these viruses are also called oncornaviruse.

Human pathogen retroviruses known to date include the types HTLV (human T-cell leukemia virus) I and II and HIV (human immunodeficiency virus) 1 and 2 The former are T-cell malignancy-causing pathogens, the latter cause ac­quired immune deficiency syndrome—AIDS.

AIDS manifests as a reduction of T helper cells after an average incubation time of 10 years. The collapse of cellular immunity results in occurrence of typical opportunistic infections (Pneumocystis carinii pneumonia, fungal and mycobacterial infections, CMV, and other viral infections) as well as lym­phomas and Kaposi sarcoma. Transmission is by sexual intercourse, blood and blood products, as well as prenatal and perinatal infections.

Diagnosis: HIV infections are routinely detected by serology (antibodies or viral antigen). The circulating virus count (viral load) is determined by means of quantitative RT-PCR. The AIDS diagnosis is a clinical procedure that pre­supposes positive confirmation of HIV infection.

Therapy: inhibitors of reverse transcriptase and protease.

Prevention: exposure prophylaxis when contact with blood is involved (drug addicts, healthcare staff) and sexual intercourse. Postexposure prophylaxis and prophylaxis in pregnancy with chemotherapeutics. 

Pathogen. The Retroviridae family is the classification group for all RNA viruses with reverse transcription of RNA to DNA in their reproductive cycles (RNA-dependent DNA synthesis). Only zoopathic retroviruses were known for many years. These viruses cause various kinds of tumors in animals. In 1980, retroviruses were also discovered in humans. This virus family includes seven genera, three of which play significant roles in human medicine:

-HTLV-BLV retroviruses, including HTL viruses types I and II and the bo­vine leukemia virus.

-Spumaviruses, which only occur in animals, two of which are (probably) from humans.

-Lentiviruses, with the human pathogens HIV 1 and 2, maedivirus (pneu­monia), and visnavirus (encephalomyelitis) in sheep, viruses affecting goats and horses, and animal immune deficiency viruses.

A human pathogen retrovirus was isolated for the first time in 1980 from adults suffering from T-cell leukemias. It was designated as HTLV I (human T-cell leukemia virus). A short time later, a virus was isolated from hairy cell leukemia patients and named HTLV II.

HTLV I is found in adults with T-cell malignancy as well as in patients with neurological diseases (myelopathies). HTLV II appears to be associated with T-cell malignancy and other lymphoproliferative diseases. Its own etio­logical role is still under discussion.

Here is a summary of the human pathogenic aspects of HIV including its relation to acquired immune deficiency syndrome (AIDS).

The viral RNA genome, which is integrated in the genome of the host cell, contains the following genes and regulatory sequences (. Fig. 8.14):

Genes essential to viral replication:

-tat gene: “transactive transcription,” enhances the transcription and thus the expression of viral proteins by binding to the TAR (transactivation responsive region) in the LTR.

-rev gene: posttranscriptional activator for splicing and transport of viral mRNA (production of structural proteins).

-LTR sequence: promoter and enhancer elements.

Structural genes:

-gag gene: group-specific antigen.

-pol gene: codes for the reverse transcriptase, a protease and the integrase.

-env gene: envelope glycoprotein (gp).

Genes not essential to viral replication:

-Virus infection factor (vif): makes the virus more infectious.

-“Negative” factor (nef): inhibits or activates viral transcription as re­-quired, influences T-cell activation, reduces CD4 expression.

-vpr: controls rate of replication.

 -vpx: only in HIV 2, controls rate of replication.

- vpu: only in HIV 1, contributes to viral release, increases CD4 turnover.