The genus of the family Retroviridae consists of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.

• Bovine lentiviruses (e.g. Bovine immunodeficiency virus, Jembrana disease virus)
• Equine lentiviruses (e.g. Equine infectious anemia virus)
• Feline lentiviruses (e.g. Feline immunodeficiency virus)
• Ovine/caprine lentivirus (e.g. Caprine arthritis-encephalitis virus, Ovine lentivirus, Visna virus)
• Primate lentivirus group
  • Human immunodeficiency virus (HIV) types 1 – 3
  • Simian AIDS retrovirus SRV-1
  • Human T-cell lymphotropic virus type I and II
  • Simian immunodeficiency virus

Most of the lentiviral vectors presently in use are HIV-derived vectors. The cis- and trans-acting factors of lentiviruses are often on separate plasmid vectors, with packaging being provided in trans. The vector constructs contain the viral cis elements, packaging sequences, the Rev response element (RRE), and a transgene.

Lentiviral Pseudotyping

Replacement of the HIV envelope glycoprotein with VSV-G provides a broad host-range for the vector and allows the viral particles to be concentrated by centrifugation. Lentiviruses can also be pseudotyped with other envelope proteins, such as the envelope of rabies virus.

What are the hazards?

In terms of the pathogenesis of lentivirus, some key properties are:

1. Lentiviruses persist lifelong. This is a function both of their ability to integrate into the host chromosome and of their ability to evade host immunity. This ability to evade host immunity may be related both to the high mutation rates of these viruses, and to their ability to infect immune cells (macrophages, and in the case of HIV, T-cells).
2. Lentiviruses have high mutation rates. Lentiviruses replicate, mutate and undergo selection by host immune responses.
3. Infection proceeds through at least three stages.
   1. Initial (acute) lentivirus infection is associated with rapid viral replication and dissemination, which is often accompanied by a transient period of disease.
   2. This is followed by a latent period, during which the virus is brought under immune control and no disease occurs.
   3. High levels of viral replication then resume at some later time, leading to disease.

Acute infection with human lentiviruses can appear as non-specific “flu-like” and “mononucleosislike” symptoms, including myalgia, arthralgia, diarrhea, nausea, vomiting, headache, hepatosplenomegaly, weight loss and neurological symptoms.

Epidemiology

Transmitted from person to person through direct exposure to infected body fluids (blood, semen) sexual contact, sharing unclean needles etc.; transplacental transfer can occur.

Laboratory Hazards

Direct contact with skin and mucous membranes of the eye, nose and mouth; accidental parenteral injection; ingestion; hazard of aerosols exposure unknown; insertional mutagenesis; integration and expression of oncogenes or potential oncogenes.

The above PPE are often required IN ADDITION to working in a certified Biosafety Cabinet.

Susceptibility to disinfectants: Susceptible to many disinfectants – 1% sodium hypochlorite, 2% glutaraldehyde, formaldehyde, ethanol

Use in Lab: BSL-2, BSL-2+ (with amphotropic or VSV-g envelope), BSL-3 (large volumes)

BSL-2+: Defined as working with BSL-2 agents using BSL-3 practices, including, but not limited to: no bench-top work allowed—all work done in a Biosafety Cabinet; decontamination with appropriate disinfectant to be done immediately following any work with biohazardous materials; required use of lab coats and other appropriate PPE, including gloves and eye protection; use of physical containment devices (such as sealed centrifuge rotors) for all activities, opening of these devices only in a Biosafety Cabinet, and decontaminating them immediately after use.

Use with Animals: For use of third generation (or higher), four plasmid Lentiviral vector systems

• In rodents without human cells present: ABSL-2 for 48 hrs, then ABSL-1
• Transformed/transfected cells cultured in vitro for >48 hrs prior to injection into rodent: ABSL-1+

ABSL-1+: – BSC and other safety equipment as needed – Practices: RAF staff can do husbandry, cage changing