Virus-Host Gene Interactions Define HIV-1 Disease Progression

• Authors: Daniela C. Monaco, Emory University; Zachary Ende, Emory University; Eric Hunter, Emory University
• Journal Title: Current Topics in Microbiology and Immunology
• Volume: Volume 407
• Publisher: Springer Verlag (Germany) | 2017-01-01, Pages 31-63
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/82_2017_33
• Subjects: Health Sciences, Oncology; Biology, Genetics; Biology, Virology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Genetics & Heredity; Virology; SIMIAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS MOLECULAR CLONES; TRANSMITTED FOUNDER HIV-1; MUCOSAL HOMING RECEPTOR; T-LYMPHOCYTE RESPONSE; HETEROSEXUAL TRANSMISSION; REPLICATION CAPACITY; VIRAL-LOAD; ESCAPE MUTATIONS; TYPE-1 INFECTION

Abstract

In this chapter, we will review recent research on the virology of HIV-1 transmission and the impact of the transmitted virus genotype on subsequent disease progression. In most instances of HIV-1 sexual transmission, a single genetic variant, or a very limited number of variants from the diverse viral quasi-species present in the transmitting partner establishes systemic infection. Transmission involves both stochastic and selective processes, such that in general a minority variant in the donor is transmitted. While there is clear evidence for selection, the biological properties that mediate transmission remain incompletely defined. Nevertheless, the genotype of the transmitted founder virus, which reflects prior exposure to and escape from host immune responses, clearly influences disease progression. Some escape mutations impact replicative capacity, while others effectively cloak the virus from the newly infected host’s immune response by preventing recognition. It is the balance between the impact of escape mutations on viral fitness and susceptibility to the host immunogenetics that defines HIV-1 disease progression.