Lentivirus

From MicrobeWiki, the student-edited microbiology resource
Revision as of 15:40, 16 September 2010 by BarichD (talk | contribs)
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to: navigation, search
This student page has not been curated.

A Microbial Biorealm page on the genus Lentivirus

Classification

Higher order taxa

Viruses; ssRNA positive-strand viruses; Retroviridae; Lentivirus

Description and significance

Lentiviruses are among the most intensely and extensively studied group of viruses. They are found worldwide and infect a broad array of animal species. Historically, lentiviruses have been investigated longer than any other virus group. The first viral etiology ascribed to an animal disease was a lentivirus. The diseases associated with lentiviral infections range from benign and subclinical to severely debilitating and lethal. The diverse group of viruses that compose the lentiviruses have many common and distinctive features. Among the common features is tropism for cells from the monocyte/macrophage lineage. Infection of macrophage affords this assorted group of viruses many evolutionary advantages, including a potential hiding place from the infected host's immune system (1). (source: Lentiviruses and Macrophages: Molecular and Cellular Interactions)

Genome structure

The lentiviruses are retroviruses. These are RNA viruses that are replicated in a host cell via the enzyme reverse transcriptase to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA (2). (source: Retroviruses: Molecular Biology, Genomics and Pathogenesis)

Pathology

Infections are characterized by immune system dysfunctions following sometimes lengthy incubation periods. The viruses in this genus include primate lentiviruses such as HIV as well as animal lentiviruses including equine infectious anemia virus (EIAV). An intriguing feature of lentiviruses is their ability to hijack macrophages so that they are simultaneously involved in the dissemination and control of virus spread throughout the host, leading to disease induction and/or transmission to a new host. (source: Lentiviruses and Macrophages: Molecular and Cellular Interactions)

Macrophage biology

Macrophages possess elaborate sensors for pathogens and have evolved complex chemically mediated interactions with other components of the immune system. Macrophage precursors differentiate into multiple end-stage specialised cell types in mammals, each suited for specific roles in homeostasis and defence. Macrophages play a role in the coordination of immune defences and employ specific mechanisms to address different kinds of threats to the parent organism. Research in macrophage biology is at a particularly exciting stage with new defence pathways still in the process of discovery. Macrophages are critically involved in disease in humans and animals because of their roles both in chronic inflammatory diseases and during infections by important pathogens, including lentiviruses (1).

Human immunodeficiency virus HIV

Human immunodeficiency viruses (HIV-1 and HIV-2) have evolved from a reservoir of African non-human primate lentiviruses, the simian immunodeficiency viruses. In contrast to the epidemic nature of HIV-1 infections, HIV-2 is restricted in its worldwide distribution, with the lower viral loads established in asymptomatic infection a significant cause of its diminished transmission efficiency. HIV-2 is also much less pathogenic than HIV-1 and results in a reduced rate of progression to AIDS despite a substantial proviral burden. The majority of patients remain asymptomatic and die of causes unrelated to immunodeficiency (1,2).

The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of coreceptor usage (including CD4-independence) may assist the virus in its adaptation to avoid innate restriction factors present in host cells. Adaptation to use normal cellular machinery to enable transmission and productive infection has also aided the establishment of HIV-2 replication in humans. A survival strategy for any infectious agent is not to kill its host but ultimately become a commensal organism. Having achieved a low pathogenicity, over time, variants more successful at transmission will be selected (1,2).

Simian immunodeficiency virus SIV

Simian immunodeficiency viruses (SIVs) naturally infect African nonhuman primates. Cross-species transmissions of SIVs from naturally infected chimpanzees/gorillas and sooty mangabeys are at the origin of HIV-1 and HIV-2, respectively. Experimental or accidental transmission of SIVsmm to different species of macaques resulted in the development of AIDS animal models. Differently from humans and macaques which, upon infection, invariably progress to AIDS, natural SIV hosts are generally spared of disease progression. Pathogenic and nonpathogenic SIV infections share some major features, such as a very active viral replication during both acute and chronic infection, a significant acute depletion of CD4+ T cells, which is more prominent at mucosal sites, and a partial control of the virus by both adaptive and innate immune responses. Although SIVs have the potential to infect macrophages, the bulk of viral replication in vivo is supported by CD4+ T cells in both pathogenic and nonpathogenic infections. A better understanding of the mechanisms underlying the lack of disease in natural hosts for SIV infection will likely provide important clues as to the pathogenesis of AIDS in HIV-infected individuals (1).

Felid immunodeficiency virus FIV

Lentiviruses are widespread pathogens of primates, ungulates and felids. While the ungulate lentiviruses induce a disease state typical of a chronic inflammatory condition, the felid and primate lentiviruses induce an immunodeficiency characterised by a progressive depletion of CD4+ T helper cells. FIV infection of the domestic cat may lead to a spectrum of diseases, ranging from a rapid, acute-onset immunodeficiency to a chronic wasting disease with concomitant neuropathology and persistent recurring opportunistic infections. Here, we examine the host and viral determinants of FIV cell tropism and pathogenicity. The virus targets activated CD4+ T cells selectively by interactions with its primary receptor, CD134 and co-receptor, CXCR4 (1).

Equine infectious anemia virus EIAV

Wendy Maury and J. Lindsay Oaks Equine infectious anemia virus (EIAV) is an ungulate lentivirus related to human immunodeficiency virus (HIV). Much of the understanding of lentiviral infection of macrophages comes from HIV studies that have provided insights into molecular regulation of all lentiviruses. However, numerous aspects of the life cycle of each lentivirus are unique and associated with specific pathological consequences. In vivo EIAV is primarily if not exclusively a macrophage-tropic virus. As a consequence of this targeted tropism, EIAV causes an acute and sometimes fulminant disease associated with high-titered viremia with no associated immunodeficiency. Investigations have only begun to unravel the molecular mechanisms leading to cell-specific replication of EIAV (1).

Small ruminant lentiviruses SRLV

The Visna-Maedi virus (VMV) and the caprine arthritis encephalitis virus (CAEV) were considered to be specific pathogens of sheep and goats, respectively. The finding that these lentiviruses frequently cross the species barrier between sheep and goats, and vice versa, has changed our view of the epidemiology of these viruses and they are now referred to as small ruminant lentiviruses (SRLV).

Monocytes-macrophages and dendritic cells are the main target cells of CAEV. Monocytes carrying the lentiviral provirus in their genome show little or no viral transcription. These latently infected cells are believed to function as "Trojan horses", capable of spreading the virus to different organs, while eluding the host immune response. The terminal maturation of monocytes to macrophages activates the expression of the transcription factors that, by interacting with the control elements in the viral LTRs, promote the production of infectious virus. The LTR sequences of different SRLV isolates are quite heterogeneous and may control the tissue-specific replication of these viruses and their virulence. SRLV replicate unrestrictedly and to high titers in differentiated macrophages in vitro, whereas in vivo virus replication is tightly controlled by mechanisms involving innate immunity and the adaptive immune system, and the intrinsic resistance of cells to retrovirus replication.

SRLV manipulate the expression of different cytokines in infected cells and modulate the cytokine response of these cells to stimulation of the various receptors involved in recognizing pathogen associated molecular patterns (PAMPS). The genetic background of animals influences the clinical outcome of SRLV infection which, in contrast to HIV infected humans, is mainly benign in the majority of infected animals. Most animals therefore fulfill the criteria defining long-term non-progressors. Finally, the various strategies adopted by SRLV to manipulate the aforementioned immunological and non-immunological antiviral mechanisms directly influence the efficacy of vaccination strategies as documented by the paradoxical effects induced by experimental vaccines on viral load and pathological manifestations in vaccinated and challenged animals (1).

Bovine lentivirus

Infections with the bovine lentiviruses, bovine immunodeficiency virus (BIV) or Jembrana disease virus (JDV) represent the extremes of lentivirus induced disease. BIV has a broad cell tropism and causes a mild lymphoproliferative disorder with low viral titres and no reproducible disease sequelae. JDV has a more restricted cell tropism than BIV and infects Bali cattle in Indonesia, replicating to high viral titres during an acute disease period characterized by lymph node enlargement, leucopaenia and high rectal temperatures. There are similarities and differences between these two genetically and antigenically closely related viruses and between other lentiviruses (1).


References

1. Desport, M. 2010. Lentiviruses and Macrophages: Molecular and Cellular Interactions

2. Kurth, R. and Bannert, N. 2010. Retroviruses: Molecular Biology, Genomics and Pathogenesis