HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread

Abstract

So far, only two retroviruses, human immunodeficiency virus (HIV) (type 1 and 2) and human T-cell lymphotropic virus type 1 (HTLV-1), have been recognized as pathogenic for humans. Both viruses mainly infect CD4+ T lymphocytes. HIV replication induces the apoptosis of CD4 lymphocytes, leading to the development of acquired immunodeficiency syndrome (AIDS). After a long clinical latency period, HTLV-1 can transform lymphocytes, with subsequent uncontrolled proliferation and the manifestation of a disease called adult T-cell leukemia (ATLL). Certain infected patients develop neurological autoimmune disorder called HTLV-1-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP). Both viruses are transmitted between individuals via blood transfusion, tissue/organ transplantation, breastfeeding, and sexual intercourse. Within the host, these viruses can spread utilizing either cell-free or cell-to-cell modes of transmission. In this review, we discuss the mechanisms and importance of each mode of transmission for the biology of HIV-1 and HTLV-1.

Keywords: HIV-1; HTLV-1; cell-to-cell transmission; cytonemes; filopodia; replication-dependent vectors; virological synapse.

Figure 1

HIV-1 and HTLV-1 virion composition. Subunit names of structural and nonstructural proteins are given for each virus. Created with BioRender (https://biorender.com/) on 26 November 2021.

Figure 2

Comparison of genome organization for HIV-1 (top) and HTLV-1 (bottom). The names of viral genes and proteins are given in lowercase and uppercase letters, respectively. The arrowheads indicate protein cleavage sites. This image was created using BioRender (https://biorender.com/) on 26 November 2021.

Figure 3

HIV-1 viral life cycle, from entry to production of mature virions. See explanations in the text. Adapted from “HIV Sites for Therapeutic Intervention” by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates, accessed on 26 November 2021.

Figure 4

A schematic demonstration of transmission-capable intercellular contacts forming (a) virological synapse (VS), (b) infectious synapse (IS), (c) viral biofilms, and (d) conduit-based mini-VS. Created with BioRender (https://biorender.com/) on 20 December 2021.

Figure 5

Scanning electron microscopy of HTLV-1 chronically infected cells, MT2, co-cultured with Raji B cells at a 1:5 ratio for 1 h (Mazurov D, unpublished data). Budding virions can be seen on the surfaces of the MT2 cell body and thin protrusions.