HIV and SIV infection: the role of cellular restriction and immune responses in viral replication and pathogenesis

Abstract

The human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have a long biological history. Both viruses evolved from Africa and remnants of them can be found in the ‘fossil record’ of several species in which they are not endemic. SIV remains endemic in several species of monkeys in Africa where it does not cause immune deficiency. HIV and SIV actively replicate within humans and Asian non‐human primates, despite cellular and genetic viral restriction factors and genes, and at times robust innate and adaptive immune responses. While Lentiviruses are considered ‘slow viruses’ it is clear in humans and susceptible Asian monkeys that virus production is rapid and highly active. This results in a massive loss of CD4+ memory effector T cells early after infection and a continued race between viral evolution, cytotoxic lymphocytes, and failed neutralizing antibody responses. Concurrently, HIV and SIV can infect monocyte/macrophage populations in blood and more importantly in tissues, including the central nervous system, where the virus can remain sequestered and not cleared by anti‐retroviral therapy, and hide for years. This review will discuss species and cellular barriers to infection, and the role of innate and acquired immunity with infection and pathogenesis of HIV and SIV in select species.

Mucosal and Peripheral Lin − HLA-DR + CD11c/123 − CD13 + CD14 − Mononuclear Cells Are Preferentially Infected during Acute Simian Immunodeficiency Virus Infection

“…Numerous studies (8,50,59,61) have shown that Apobec3G could restrict SIV infection, whereas Sui et al (56) demonstrated that plasma viral loads inversely correlated with Apobec3G levels. Saez-Cirion et al (48) showed that intracellular restriction contributes to the intrinsic cell resistance of monocytes to HIV-1 infection, whereas Peng et al (43) showed that monocytes contain higher levels of Apobec3G than macrophages.…”

Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View

“…TRIM5 is a protein described in primates that restricts retroviral replication by interaction with the capsid to prevent uncoating [332]. However, human TRIM5 shows only modest activity against HIV, though a single amino acid substitution in TRIM5 confers potent inhibitory action [333].…”

mTOR as a multifunctional therapeutic target in HIV infection

“…HIV is a genetically related member of the Lentivirus genus of the Retroviridae family that shows a particular tropism for CD4 + T cells [15]. However, the CD4 antigen alone is not sufficient for virus entry, because a co-receptor is necessary to gain access into the cells.…”